The Most Devastating Grey's Anatomy Breakups

Grey's Anatomy is one of a few television shows that have stood the test of time and have, throughout their seasons on the small screen, made the viewers fall in love with the characters like they were their own friends and family. Having been on ABC since 2005Grey's Anatomy has cycled through what feels like a million characters and, as a result, a lot of on-camera relationships.

As diehard fans know, Grey's Anatomy and writer/creator Shonda Rhimes have made viewers endure some of the worst heartbreaks due, in part, to the love stories that have come to an end. And, of course, even people who don't watch the show know of the romance between Meredith Grey and Derek Shepherd and the devastating end to their love story (which we'll get into later). 

From Meredith and Derek's very first split to the infuriating end to Alex and Jo, here are the most devastating Grey's Anatomy breakups.

Jackson and April's breakup might be the worst in Grey's Anatomy history

Everything seems to be worse and far more dramatic when there's a pregnancy involved, and that's just what the situation was when Jackson and April ended their marriage. After a whirlwind romance that resulted in April leaving her fiancé at the altar for Jackson, the couple's relationship went downhill. And following a tragic pregnancy that resulted in their death of their baby, April and Jackson were never the same.

The two decided to get divorced — but in classic Grey's Anatomy fashion, April found out she was pregnant again before they signed their papers. She signed anyway — even knowing the news — and by the time Jackson found out about their second chance at a family, their relationship exploded in a very public way. In Season 12, Episode 5, "I Am Not Waiting Anymore," Jackson and April have at it in the middle of the hospital. "You don't think a pregnancy would have factored into my decision to move forward with the divorce?" Jackson asked his ex. "I knew it would, but you didn't want to stay with me," April responded. Talk about a heart-breaking moment.

Grey's Anatomy's Mark and Lexie's on-again, off-again relationship ended in the worst way

If there is one Grey's Anatomy couple that none of us will ever be able to recover from, it's Mark and Lexie. They could never really get their relationship timing right, and there always seemed to be something that got in the middle of their romance. In Season 6, Mark found out that he was going to be a grandfather, and he invited his pregnant daughter to live with him without talking to Lexie about it first. 

Understandably, the situation completely threw Lexie for a loop, and she ended their relationship as a result in the Season 6 episode "Blink." "I was barely ready to move in with you," she told Mark, "never mind your daughter and grand-baby. I don't want this." He then admitted he'd choose his daughter over her.

Of course, for those of you who are Grey's super-fans, you know what happened in Season 8. Mark and Lexie, accompanied by the other doctors of Seattle Grace Hospital, suffered a devastating plane crash. Lexie died from her injuries, and Mark passed away shortly after. "You can't die because we're supposed to end up together. We're meant to be," Mark said to her as she died. This marked one of Grey's Anatomy's most heartbreaking moments.

We were all secretly hoping that Grey's Anatomy's Derek and Addison would figure it out

Derek Shepard and Addison Montgomery were a power couple — both doctors, both gorgeous, both accomplished. But their marriage was fraught with infidelity, and as a result, Derek escaped to Seattle and left Addison to figure out her own path. She decided to follow him and ended up in Seattle where they tried to give their marriage another shot. Ultimately, Derek found Meredith, and Addison couldn't stop getting involved with Mark (Derek's best friend). As a result, their marriage ended. 

So when Derek and Addison finally admitted that their union is over, the moment was truly crushing. In Season 3, Episode 2, "I Am a Tree," Derek sat next to Addison on a bed and said, "Our marriage is over," adding, "It's all my fault." Addison agreed that their time together had come to an end, before Derek said, "God, this is incredibly sad." And if a heartbreaking moment couldn't get any worse, Mark then emerged in a cloud of irresistible steam from the bathroom, wrapped solely in a towel. Moment even more ruined. Gotta love Grey's Anatomy.

Grey's Anatomy fans watched Bailey go through it when she and Tucker Sr. broke up

One of Grey's Anatomy's most beloved characters, Miranda Bailey suffered on screen as her marriage fell apart. Viewers really didn't see much of her husband, Tucker Sr., at all during the show — but given that the relationship made such an impact on Bailey and the choices she made, we had to include it. Since the first episode, Bailey had been known for her grit, so when Bailey told Dr. Arizona Robbins in Season 5's "Now or Never" that she was having to choose between a fellowship opportunity and her marriage, her vulnerability was striking. "My husband informed me yesterday that if I accept the peds fellowship ... he will divorce me. It's a big decision," she said, before walking away. It's a moment that stuck with a lot of Grey's fans given that Bailey had always been so in control. 

Later on, Bailey came to terms with the ultimatum that Tucker Sr. gave her, and she broke down in tears in front of Dr. Richard Webber. "I'm leaving him," she told Webber, "because a marriage that resorts to ultimatums, that's not a marriage." So even though the breakup itself wasn't seen on screen, the devastating shockwaves were felt tenfold.

Burke leaving Cristina at the altar ripped Grey's Anatomy fans' hearts out

Of all the early established couples on Grey's Anatomy that we really hoped would last, Cristina and Burke seemed like they had it in the bag. Think about it — they were both exceptional surgeons devoted to their craft; that kind of challenging lifestyle was something they could share together, and, for a while, they did. So when Burke asked Cristina to marry him, it was truly such a good moment. 

But the couple delivered one of the worst breakups in Grey's history. Cristina, played by Sandra Oh, was always hesitant about a wedding, but she eventually went through the dress-shopping and dealt with the future in-laws to make Burke happy. On the day of the wedding in the Season 3 finale, she had a "momentary freak-out" but was ready to commit, and that's when Burke dropped the worst bomb on us while at the wedding ceremony. "I'm up there waiting for you to come down the aisle, and I knew you don't want to come," he said to her, adding, "If I loved you ... I would be letting you go." Like come on, why did he do that to us!

Grey's Anatomy couple Callie and Arizona couldn't make it work no matter how hard they tried

Grey's Anatomy has been groundbreaking on a lot of levels — the show has consistently featured a racially diverse cast, has highlighted women in the workplace, and has brought same-sex couples to the screen. One such couple was Callie and Arizona, two amazing doctors who (for a time) really brought out the best in each other. But like a lot of Grey's relationships, theirs was on and then off, then on again... only to once again be off again. 

And by the time the couple had made it all the way to Season 11, despite infidelity, an accidental pregnancy, and a bunch of drama (via Bustle), Callie finally decided to walk away, and the scene in which she delivered the news to Arizona was beyond devastating. "I can see now that constantly trying to fix us is the thing that's been killing me slowly," Callie said in the episode "Bend & Break." She went on, "Maybe instead of loving you so hard, I should be myself for a while." We're all for recognizing when a relationship is no longer working, but Callie's delivery of the news with tears and mascara smudges broke our hearts.

Meredith and Derek's Season 2 breakup was too much for Grey's Anatomy fans to handle

From the first episode of Grey's Anatomy, Meredith and Derek got us invested in their relationship, leading us to have our hearts be ripped out over and over again. After Derek's wife Addison came back on the scene and the two tried to put her infidelity (and his, for that matter) behind them, Meredith reached a breaking point and delivered one of the best monologues of the show. 

"Your choice, it's simple — her or me," Meredith, played by Ellen Pompeo, started in Season 2's fifth episode, "Bring the Pain." "I'm sure she's really great. But Derek, I love you ... so pick me, choose me, love me." Honestly, it takes a considerable amount of strength to open up your heart like that to someone — especially if the outcome is unknown — so even though this exchange happened in the fictional world written by Shonda Rhimes, it remains one of the most heartbreaking and yet awe-inspiring moments. Unfortunately, the scene eventually led to Derek giving his marriage with Addison another go (which was made especially painful since he had the choice to sign divorce papers and pursue things with Meredith).

After a long, winding road, Izzie and Alex delivered one of Grey's Anatomy's worst breakups

This breakup is maybe one of Grey's Anatomy worsts. Izzie and Alex had a rocky start in their relationship, so when they finally did get together, it was a miracle. But their happiness was short-lived. Izzie was diagnosed with cancer, and Alex stayed by her side throughout (via Elite Daily). They even got married, though it was rushed, giving Izzie the perfect wedding day despite her illness. 

But when Izzie recovered and left Alex for a brief time, he finally confessed that he wanted to move on separately — and it really was devastating. In the Season 6 episode "I Like You So Much Better When You're Naked," Alex expressed how getting through Izzie's illness and being by her side proved to him that he was a good man, despite thinking the contrary for so long. "I know now that I'm good enough not to deserve this," Alex said. "Not to feel like this — not to love you so much that I almost hate you. I deserve someone who will stay." To say the scene was upsetting would be an understatement, but for those of you who are avid watchers, you know that was not the last we saw of Izzie and Alex.

It was inevitable, but Grey's Anatomy's Callie and George breaking up was still so sad

Oh, George O'Malley. Given that Grey's Anatomy has given us so many characters, it's hard to keep track and remember everyone, but George was so enduring that, even though his character didn't stay around for too many seasons, he is still one to remember. Especially given that he married Callie (who, yes, became Callie O'Malley) sort of on a whim. But despite the whirlwind that was their marriage, Callie really seemed to love George, which made his infidelity and their subsequent breakup that much more painful to watch. 

After finding out that George cheated, Callie told him that she forgave him — but in pure Grey's style, the two found themselves standing in the rain, facing the reality of their marriage in Season 4's "The Heart of the Matter." "What I did to you is unforgivable," George started off. "You don't know how to talk to me right now, you can't even look at me ... you don't forgive me." Callie conceded and told George that he's right and that she doesn't forgive him, and she then walked away. It was the ending that we all could have predicted, but it still hurt to watch.

Richard and Ellis were meant to be, so their breakup on Grey's Anatomy was rough

Back in the early days of Grey's Anatomy, one of the biggest reveals was that Meredith's mom, Dr. Ellis Grey, had a long-lasting affair with Richard Webber, the former chief of surgery at Seattle Grace. They met back in the early years of their careers and had some devastating ups and downs. A lot of their back story was told on Grey's in a series of flashbacks, and one scene between them has always stood out from the others. 

In the Season 11 episode "Only Mama Knows," viewers saw the two doctors standing by a carousel with Richard clearly ending his relationship with Ellis. "I'm sorry, I can't," Richard said. "Richard, you can't leave me," Ellis responded, before begging for him to stay. All the while, a young Meredith rode the carousel, witnessing the whole situation unfold. Meredith later recalled that after Richard ended their relationship, Ellis tried to take her own life. "Everything after that was my fault," Richard confessed to Meredith. "I made the wrong choice for the wrong reason, and there's hardly a day goes by that I don't — I'm so sorry." Talk about a heartbreak from start to finish.

Bailey and Ben's breakup in Season 7 delivered one of the saddest lines in Grey's Anatomy history

Fans of Grey's Anatomy have seen Miranda Bailey handle a lot — a divorce, a life-altering shooting, new relationships, life as a parent — but nothing came as close to the kind of heartache Miranda experienced when she broke up with Ben in Season 7's premiere episode. When Bailey shows a kind of raw emotion, it's a big deal, and, during the scene in question, she delivered a line that was devastating. 

"You are perfect," she said to Ben. "But I'm busy holding myself together with tape and glue." Sobbing, she continued, "You're too much for me right now, because I'm busy with the tape and the glue." Ugh, talk about having to break out the tissues. Ben left the devastating breakup by telling Bailey to "take care" of herself, kissing her hand, and then walking away. It's so much to handle, and honestly it's up there with one of the most (if not the most) painful Grey's breakups. 

When vulnerable, Bailey is so relatable, and she chose to focus on herself in that moment which is so commendable. But it still hurts every time we watch it.

Grey's Anatomy couple Cristina and Owen sadly wanted different things

A list of devastating Grey's Anatomy breakups wouldn't be complete with Cristina and Owen, as their breakups were some of the worst to handle. The couple were on again, off again, and then on again more times than we could count. They got married, got divorced, and then stayed together even after getting divorced — all of it was messy. But things got to a point between Cristina and Owen where they could no longer be resolved, and that's when Owen's wish to have a family became too much for Cristina to handle. 

"Am I enough, Owen?" she asked him in Season 9's finale. "Do you really believe I'll be enough?" Owen didn't respond right away, but then he nodded his head yes and quickly looked down to the floor. In his silence was the answer that Cristina needed to hear. Owen tried to tell her that she was wrong, that she was all he needed, but he couldn't convince her — let alone himself. "It already happened," Cristina eventually said, and she left. Owen and Cristina went through so much in their relationship that this breakup was especially hard to watch.

The Grey's Anatomy letter heard round the world

Despite his frat boy persona at the beginning of Grey's Anatomy, Alex became adored by everyone and that included Jo Wilson, who became his wife. They had one of his most consistent relationships throughout the show. So their breakup was beyond devastating because so many of us thought they were meant to be. But Alex found out that Izzie, who had frozen their embryos, had given birth to his kids. He made the difficult, but necessary choice to leave Jo and be with Izzie and his family in Kansas. And he wrote a letter to Jo explaining everything, which we saw in the Season 16 episode "Leave a Light On."

"You deserve more than a letter," he wrote. "This cowardice, this letter — it's officially the worst thing I've ever done." And that's saying a lot given that Alex did some pretty terrible things. Alex went on to say that Jo, of all people, should understand why he needs to be with his kids given their own traumatic childhoods. The whole scene, despite Jo and Alex not sharing screen time during the actual breakup, was devastating and is still one of the saddest Grey's moments.

Owen and Amelia were a mess on Grey's Anatomy, and their breakup was not easy to watch

Out of all the Grey's Anatomy relationships that were clearly not meant to be, Owen and Amelia's relationship was the most doomed. Owen had fought PTSD throughout the show, and Amelia was a recovering addict. Their own problems seemed to amplify, and, given that both were as messed up as the other, their marriage was not built to last. Even though most Grey's viewers could've predicted that they would break up, Owen and Amelia's ending was still painful to watch. 

"It feels like we don't know each other," Owen said in Season 14's  "Danger Zone." "I just want us to be happy," he continued. "It's ok, Owen. I know," Amelia said. Both proceeded to take off their wedding bands, giving them to each other, before embracing in a hug. 

Both Owen and Amelia — despite the devastating sadness of the scene — seemed relieved in a way, almost like they knew that they had tried and it was ok that their relationship was coming to an end. Of course, for us emotional people, that didn't make the scene any easier to watch and we recommend having an ample supply of tissues at the ready next time you watch it.