Grey's Anatomy's Most Heartbreaking Moments

ABC's Grey's Anatomy first premiered in March 2005 — and the hit medical drama has been going strong ever since. Not only did Grey's Anatomy introduce showrunner Shonda Rhimes to the television world as a force to be reckoned with, but the show also brought together a cast of characters that would go on to leave a lasting imprint on the hearts of fans across the globe.

Since its premiere, Grey's Anatomy has been the source of much delight for its viewers, as well as the reason for countless tears. The long-running series is known for subverting expectations and throwing in plot twists designed to leave fans breathless and on edge for what's going to happen next. Unfortunately, predicting what's to come in the series is a nearly impossible feat. Frankly, the only constant in the Grey's Anatomy universe is the show's wealth of emotionally gut-wrenching moments guaranteed to stick with you long after you turn off your TV. 

As any seasoned Grey's Anatomy viewer can attest, this series is best consumed with a best friend and box of tissues nearby. Here are the most heartbreaking moments to have aired on Grey's Anatomy.

In this heartbreaking Grey's Anatomy moment, the doctors have to decide who lives and who dies

In the Season 2, Episode 6 of Grey's Anatomy– titled "Into You Like a Train" — the doctors of Seattle Grace are tasked with dealing with the aftermath of a fatal train wreck. Two of their patients, Tom and Bonnie, have been impaled through their abdomens by the same pole, leaving them facing each other on the gurney, unable to move. After examining Tom and Bonnie, Dr. Burke and Dr. Shepherd realize the only way to remove the pole without killing both patients involves sliding one of them off the pole — however, that patient would likely die in the process. 

Upon further examination, Bonnie's injuries are revealed to be more extensive, and the doctors determine that Tom has a better chance of surviving surgery. Tom, who's in his 50s, refuses to let Bonnie die, as she's younger and engaged to be married. However, Bonnie bravely agrees to the procedure. After she dies during surgery, Shepherd tells her grief-stricken fiancé, "She wanted you to know that if love were enough, she'd still be here with you." 

An explosively heartbreaking Grey's Anatomy moment

"As We Know It" was the second installment in a dramatic Grey's Anatomy two-part event. The 17th episode of Season 2, "As We Know It" follows the doctors of Seattle Grace as they grapple with their own mortality after a patient is determined to have a homemade explosive device lodged in his abdomen. In the preceding episode, Hannah — the EMT originally tasked with keeping her hand inside the patient's body cavity and holding the homemade bomb steady to prevent it from detonating — buckled under pressure and evacuated the hospital floor. Without thinking, Meredith Grey placed her hand where Hannah's had been, and "As We Know It" shows the Grey's Anatomy namesake tearfully questioning her choice and contemplating her impending death. 

Though emotional, Meredith is ultimately able to keep calm and hand the bomb over to Dylan Young, a leading member of the Seattle Police Department's Bomb Squad. However, as he carefully walks down the hospital hallway with the bomb in hand, it suddenly explodes — killing him instantly. Of course, that wouldn't be the last time Meredith Grey cheated death.

Burke leaves Cristina heartbroken in this tearjerker Grey's Anatomy episode

If there's one thing Grey's Anatomy has taught fans, it's that every doctor is involved in a complicated, doomed relationship with one (or more) of their colleagues.

Such was certainly the case for Cristina Yang and Preston Burke, two Seattle Grace doctors whose tumultuous relationship seemed for a while as if it were going to have a happily-ever-after ending. Though initially opposed to the idea, Cristina finally agrees to marry Burke, and their big day was featured in the 25th episode of Season 3, "Didn't We Almost Have It All?

Moments before she's supposed to get married, Cristina finds herself panicking over her wedding vows. After a bit of encouragement from Meredith Grey, she finally begins to make her way to the ceremony. However, she's met by Burke, who tells her he thinks she's only marrying him because he wants to be married and not because she wants to be married. Despite Cristina assuring Burke she does, in fact, want to be his wife, he leaves. Later, Meredith helps a sobbing Cristina out of her wedding dress — and we can't help but sob along with her. 

Meredith and Cristina have an emotional goodbye in this heartbreaking Grey's Anatomy moment

As Grey's Anatomy fans know, Meredith Grey and Cristina Yang's friendship spawned the oft-quoted phrase found on countless mugs, t-shirts, and Pinterest boards across the Internet: "You're my person." As The Washington Post noted, those three famous words were first uttered by Cristina in Season 2, Episode 1, while explaining to Meredith she'd provided her name as an emergency contact upon an abortion clinic's request. "I put your name down," Cristina tells Meredith. She continues, "That's why I told you I'm pregnant. You're my 'person.'"

Cristina and Meredith's close friendship is what makes Cristina's departure from Seattle one of the most heartbreaking moments in Grey's Anatomy history. Before leaving the hospital to start a new job overseas, Cristina tells her best friend, "Don't get on any little, tiny planes that can crash, or stick your hand in a body cavity that has a bomb in it, or offer your life to a gunman. Don't do that." She continues, tearfully telling Meredith, "Don't be a hero. You're my person. I need you alive. You make me brave." 

Someone pass the tissues, please. 

The heartbreaking Grey's Anatomy moment in which Meredith nearly died

In the ninth season of Grey's Anatomy, Derek Shepherd tells Meredith Grey, "We've survived an unusual number of very bad things." His observation is accurate, though a bit of an understatement. As even the most casual viewer knows, the doctors of Grey's Anatomy have cheated death multiple times. This is especially true for Meredith Grey, who has somehow survived an exploding bomb, an active shooter, a plane crash, and drowning.

Despite the doctors' best efforts, Meredith technically dies after being rescued from the water in the Season 3 episode "Drowning on Dry Land." In her unconscious state, Meredith experiences visions of those who have passed on before her, including Bonnie (the young woman impaled by a pole in the train wreck), the bomb squad's Dylan Young, and Denny — Izzie Stevens' late fiancé. Just before coming back to life, Meredith suddenly sees her mother, Ellis Grey, who tells her, "You are anything but ordinary, Meredith." After an embrace, Ellis tells her daughter to run — and at Seattle Grace, Meredith's heart starts beating once again. Unfortunately, as we later learn, her mother has passed away. 

This heartbreaking Grey's Anatomy moment claimed multiple lives

Grey's Anatomy fans are no strangers to being kept on the edge of their seats by the ABC medical drama — and the Season 6 installments "Sanctuary" and "Death and All His Friends" are two of the series' most suspenseful (and heartbreaking) episodes. 

In "Sanctuary," Meredith Grey is happy to discover she's pregnant with Derek Shepherd's child. However, before she has the chance to tell her beau, an active shooter begins terrorizing the hospital. The gunman, a disgruntled widower of a deceased patient, blames Derek for his wife's death and has come to Seattle Grace intending to kill the neurosurgeon. At the end of "Sanctuary," the assailant comes face to face with Dr. Shepherd, shooting him. However, in "Death and All His Friends," Cristina Yang and Jackson Avery work together to perform a lifesaving surgery on Derek, despite the gunman threatening to kill Cristina if she continued operating. 

Tragically, the shooting claims multiple lives, including those of Charles Percy, Reed Adamson, and various other hospital employees. And, in one final knife to the heart, the stress of witnessing Derek's near-death experience causes Meredith to miscarry her pregnancy. 

Teddy and Henry's love story comes to an end in this heartbreaking Grey's Anatomy moment

Dr. Teddy Altman makes her first appearance in Grey's Anatomy Season 6, eventually meeting her future love interest Henry Burton in Season 7. Uninsured, Henry's von Hippel-Lindau syndrome has left him needing surgery he can't afford. As the doctor grows more attached to her patient, Teddy proposes that she and Henry wed to ensure his surgery will be covered by her insurance, and the two are soon pronounced husband and wife.

Initially opposed to an actual romantic relationship with Henry, Teddy continues to treat her now-husband as a friend/patient. However, despite agreeing to move to Germany with a man she's been dating, Teddy realizes she's genuinely falling in love with Henry, and the two decide to give their relationship a fighting chance. 

After a tumor is discovered in Henry's heart, he dies during the risky surgery to remove it. When Cristina breaks the news to Teddy, the grieving doctor forces her to say the words "Henry is dead," so that she'll know it's real. Years after the heartbreaking scene first premiered, it's still nearly impossible to watch it without bursting into tears

In this heartbreaking Grey's Anatomy moment, Cristina and George bond over their shared grief

The doctors on Grey's Anatomy are no strangers to death. After all, in the course of the show's multi-season run, the docs have lost plenty of patients to various illnesses and accidents. However, no matter how familiar one might be with illness and death, there's only so much preparing a person can do for the death of a parent. This is why seeing George O'Malley grapple with the loss of his beloved father is one of the most heart-wrenching moments to ever take place on Grey's Anatomy

After George makes the decision to remove his father's life support following a failed surgery, Cristina Yang finds her grieving friend standing outside the hospital. In one of Grey's Anatomy's most moving monologues, Cristina tells George, "There's a club. The Dead Dads Club. And you can't be in it until you're in it." She continues, "My dad died when I was 9. George, I'm really sorry you had to join the club."

When George says he doesn't know "how to exist in the world" without his father, Cristina replies, "Yeah, that never really changes." Cue the waterworks.

Meredith begs Derek to pick her in this heartbreaking Grey's Anatomy moment

Meredith Grey and Derek Shepherd's love story will forever be known as one of television's greatest will-they, won't-they sagas, comparable to Friends' Ross and Rachel and The Office's Jim and Pam — though much more dramatic, of course. 

Grey's Anatomy is a treasure trove full of quotes that have found new life on Pinterest boards all across the Internet. As fans know, arguably the most famous quote from the show's run thus far is a six-word piece of dialogue delivered by Meredith in a last-ditch effort to rekindle her relationship with Derek, which was put on hold following the surprise appearance of his estranged wife, Dr. Addison Montgomery-Shepherd. 

In her monologue to Derek, Meredith tells the surgeon he has to make a choice — her or his wife. And while Meredith says she's sure Addison is "great," she tells Derek she loves him "in a really, really big" way. She expands on her feelings, finally concluding her speech with the now-famous line, "Pick me. Choose me. Love me." The rest, as they say, is (medical drama) history. 

This heartbreaking moment changed the Grey's Anatomy universe forever

In the penultimate episode of Grey's Anatomy Season 8, a small plane crashes while carrying several doctors to work on a conjoined twins case in Boise, Idaho. The final episode of the season, "Flight," follows those surgeons –  Meredith Grey, Derek Shepherd, Cristina Yang, Mark Sloan, Lexie Grey, and Arizona Robbins — as they deal with the aftermath of said plane crash. 

Lexie, Meredith's half-sister and Mark's love interest, is trapped under the plane and fading quickly. Though she realizes she's dying, Mark refuses to believe he could lose her and insists she stay alive so they can get married and start a family together. He tells her the two of them are "meant to be," and, in a heart-wrenching moment, Lexie takes her final breath and whispers back to him, "Meant to be."

Mark himself nearly dies after a cardiac event, but his colleagues are able to stabilize the plastic surgeon until they're rescued and taken back to Seattle Grace. After a brief surge of health, Mark ultimately succumbs to his injuries. Later, the hospital is officially renamed Grey Sloan Memorial Hospital to honor Lexie and Mark.

Derek narrates his own death in this heartbreaking Grey's Anatomy episode

As fans of Grey's Anatomy know, Derek Shepherd did eventually pick, choose, and love Meredith Grey. However, their romance wasn't all smooth sailing. Unfortunately, as revealed in Season 11, Derek's untimely death brought their love story to a crashing halt. 

In the tearjerking episode "How to Save a Life," Derek stops his vehicle to help at the scene of an accident, only to be hit by a semi truck when he returns to his car to leave (via Entertainment Weekly). As he's admitted to the emergency department at Dillard Medical Center, Derek's internal monologue serves as a voice-over. Though he's unable to speak, he's coherent enough to realize he needs a head CT. However, the doctors at Dillard Medical Center fail to order one, and Derek realizes he's going to die as he's being prepped for an emergency craniotomy. 

Later, Meredith arrives at Dillard Medical Center and gives permission for Derek to be taken off life support, as his chances of recovering are slim to none. And, when Derek died, so did our belief in true, made-for-television love. We'll always miss you, McDreamy. 

No one saw this heartbreaking Grey's Anatomy moment coming

George O'Malley remains one of the most beloved characters in the Grey's Anatomy universe, even though he last appeared on the medical drama in 2009. Throughout his four years on our television screens, George transformed from a bumbling, well-meaning intern to a confident trauma surgeon. However, in Grey's Anatomy Season 5, George makes the surprise decision to leave his colleagues at Seattle Grace and join the U.S. Army. 

While George's departure was definitely shocking, no one could have predicted what happened next. In the Season 5 episode "Now or Never," Izzie Stevens nearly dies following a surgical procedure to remove a tumor on her brain. At the same time, Meredith Grey realizes that "John Doe," a patient unrecognizable after being hit by a bus, is George. While Meredith, Derek Shepherd, and Owen Hunt try to save George's life, an unconscious Izzie imagines she's seeing George — her best friend — on the other side of the elevator doors. As Meredith's voiceover reminds us to look around at our lives before they're gone, it becomes clear George has died. 

And our hearts have never recovered. 

Our hearts shattered for Jackson and April in this heartbreaking Grey's Anatomy moment

Jackson Avery and April Kepner's relationship will forever be known in Grey's Anatomy history as one of the show's most memorable — and surprising — couplings. Considering April is a devout Christian and Jackson is openly skeptical about the existence of God, one might think a relationship between these two would be impossible. However, opposites attract — and it doesn't take long for the two close pals to fall head over heels in love with each other and eventually elope

In Season 11, Jackson and April are delighted to discover they're pregnant. Unfortunately, however, their joy is soon overshadowed by the news that their unborn child has a fatal birth defect. Together, the couple decides to give birth to their son — Samuel Norbert Avery — and make the most of his tragically short amount of time on Earth. Little Samuel's birth, as well as his heartbreaking death, are featured in the aptly titled Season 11 episode "All I Could Do Was Cry." Be warned — the moment Samuel squeezes April's finger before he passes away is perhaps the ABC medical drama's single most devastating moment. 

Izzie was never the same after this heartbreaking Grey's Anatomy moment

Though Izzie Stevens, played by Katherine Heigl, has seemingly disappeared from the Grey's Anatomy universe for the foreseeable future, her greatest tragedy remains one of the show's most heartbreaking moments. 

In Grey's Anatomy Season 2, the model-turned-doctor falls in love with Denny Duquette, a charming patient with a congestive heart failure diagnosis. In an effort to ensure a heart transplant for Denny, Izzie cuts his LVAD wire, which fast-forwards the transplant process, and Denny proposes to Izzie before coding. Dr. Erica Hahn is able to successfully perform the transplant and save Denny's life

Later that night, during a hospital-wide prom organized for Dr. Richard Webber's sick niece, Izzie makes her way to Denny's room, wearing a (now-iconic) dusty rose evening gown. Unfortunately, she finds Denny has died since she last saw him, likely having suffered a post-surgery stroke. Sobbing, she clings to her late fiancé until Alex Karev gently carries her away. 

Needless to say, Izzie was never the same after losing the love of her life — and neither were we.