The Most Heartbreaking Character Exits on Grey's Anatomy, Ranked

The surgical resident is one of the surgeons who joins the main cast during the Mercy West merger storyline in season six. She quickly gets into the romantic entanglements, flirting with Karev and hooking up with Mark Sloan, all while being oblivious to her pal Charles Percy's massive crush on her. But, in the end, she never gets to develop much as a character before she's the first to be shot in Gary Clark's shooting spree. It's a devastating and unforgettable episode, but her character's death is instant, and her legacy is, sadly, unimpactful.

The ex-Mercy Wester never quite became a major part of the main cast, but his actual departure ranks above those of more significant characters simply for the tragic, drawn-out way it happens. During the hospital shooting spree, Charles is shot by Gary Clark, but unlike Reed, he doesn't die right away. Instead, he and Bailey, along with their patient, work to try to staunch the bleeding and get him to an OR where Bailey can try to save his life. It's grueling work, and their efforts all turn out to be in vain when they get to the elevators and discover they're shut down because of the lockdown. Charles realizes what this means and slowly dies as Bailey and their patient Mary comfort him.

Always a polarizing character, Izzie was one of the original "MAGIC" five interns, and she went through some major ups and downs during her time on the show. After barely surviving cancer and losing her best friend, Izzie struggles to try to return to normal. Ultimately, her exit is more shocking and frustrating than sad, as she leaves Seattle and breaks up with her husband Alex via letter.

After twelve seasons, Callie eventually departs Seattle for New York when her girlfriend at the time gets a prestigious grant. It's not necessarily sad that she's leaving for a new opportunity, but it's very sad how the resulting custody battle causes enormous pain for her, Arizona, and their daughter Sofia. Fortunately, the bittersweet ending for Callie's time on the show has a relatively happy outcome, as Arizona eventually leaves Seattle too, joining Callie in New York, where it's hinted they're trying to rebuild their family.

This one hurt, especially with how unexpected it was. One minute, DeLuca is trying to track down a human trafficker he's suspected for a long time, and the next, he's stabbed and bleeding out in front of his sister Carina. At first, it seems like his friends might be able to save him, but then we see him show up on Meredith's "beach" between life and death. After exchanging a few sweet but heartbreaking words with Meredith, he reassures her that she'll be fine, and then runs to where his mother is waiting to walk him into the afterlife. It's a brutal ending for a character who went through a lot during his time on the show.

You'd think we'd have learned not to get too attached to characters who are also patients, but Henry managed to break our hearts nonetheless. Henry is first introduced as a chronic patient with a condition that makes him grow tumors. When Teddy Altman finds out he needs insurance, she impulsively offers to marry him so that he can use hers. It starts out as a marriage on paper only, then develops into a close friendship and eventually a real romance. That's what makes it all the more heartbreaking when, just as they start to plan a long-term future, Henry is rushed into the OR with what turns out to be an inescapably fatal condition — and Cristina has to operate, not knowing who he is until after he dies.

Alzheimer's has been a constant presence on Grey's, from Ellis Grey and Meredith's fears of developing it herself, to the research of the neurosurgeons. It's particularly heartbreaking to watch Adele Webber's decline as she slowly loses her memories and her sense of self. In the end, her husband Richard is left to grieve her on the very same night that he's trying to be a supportive friend at Bailey and Ben's wedding.

Burke's exit is less sad for him and sadder for the impact it had on everyone else. At his planned wedding to Cristina, he leaves her at the altar and just leaves town forever. Watching Cristina sob over her lost love — while also repeating, "I'm free, I'm free" — as Meredith cuts her out of her wedding dress is definitely one of the most iconic and devastating Grey's moments.

Ellis Grey is one of those characters who is so, so complicated. On the one hand, she's a very difficult and demanding mother to Meredith. Over the first couple of seasons, we see both the difficulty Meredith has with caring for Ellis, who now has Alzheimer's, and flashbacks to Ellis prioritizing her career over her daughter. Ellis's death, however, packs a major gut punch. During the ferry-boat storyline in season 3, during which Meredith nearly drowns, Meredith is visited in the not-quite-afterlife by several figures from her past. As she's making the decision whether to live or die, Ellis appears, urges her to live, and reminds her that she is extraordinary. When Meredith wakes up, she discovers that Ellis has died, and her pain is what sends us into tears.

The first patient who really becomes a character, Denny, is also the first major death that broke our hearts on Grey's. The young heart patient quickly befriends his doctors and falls in love with Izzie. When his condition takes a turn for the worse, Izzie risks her career to cut his LVAD wire and move him up the transplant list. It works at first, and he gets a new heart and proposes to Izzie, who accepts. Alas, their fairy-tale ending was not to be: when Izzie stops by to show him her "prom" dress ahead of a big event, she finds that he died suddenly from an unexpected complication. We'll never be able to listen to "Chasing Cars" without sobbing.

We never thought we'd have to lose McSteamy! Mark's death is all the crueler for the bit of hope we're given before it's snatched away. Initially, during the plane crash, Mark seems to be one of the least injured, although he's devastated by comforting Lexie Grey as she dies. In the weeks after their rescue, however, his condition plummets, and he eventually goes to where, as he tells Callie, Lexie is waiting for him. The one comfort comes several years later, when Mark and Lexie both visit Meredith on her "beach" — turns out, Mark was serious and Lexie really was waiting for him on the other side.

Oh, Little Grey, we still cry when we think about this death! Meredith's little sister starts out as the hyper, perky counterpart to her "dark and twisty" half-sister, but she slowly becomes a fascinating and complicated character. Her on-and-off romance with Mark also becomes one of the show's great, epic loves. Sadly, they never get their happily-ever-after, as Lexie gets pinned beneath the wreckage during the season eight plane crash finale. Mark holds her hand and narrates the life they should have had in her final moments, in a scene that is impossible not to cry through while watching.

Sweet, nerdy, awkward George is the gentlest of the five original interns and is pretty much the heart of the group. At first, we're tricked into thinking that his exit is going to be one that leaves the door open for a return when he signs up to become an Army doctor like Owen near the end of season five. Later, the doctors are treating a "John Doe" who got dragged by a bus after pushing a woman out of the way. "John Doe" can't speak, but he manages to trace a message into Meredith's hand: "007," George's first-year nickname. His friends try to save him, but it's too late, and George's soul encounters Izzie's on an "elevator" between life and death as they both code at the same time. While Izzie survives, George does not, and it's a gut punch for sure.

One of the saddest deaths on Grey's is the death of a character who lived only briefly. April and Jackson find out that they're going to have a baby, but their joy turns to grief when they learn that their son has a rare bone disease that is incompatible with life. April is induced early, and she and Jackson are able to name their son Samuel and hold him for the few minutes of his life. It's a completely devastating tragedy that is incredibly difficult to watch.

There is nothing outright "sad" about Cristina's departure, but it broke our hearts nonetheless. After realizing that she'll never be able to win a Harper Avery while working at an Avery-owned hospital, Cristina takes up an offer from her ex Burke to take over his cutting-edge institute in Switzerland. It's a massive career move and a happy future for ambitious, brilliant Cristina. Still, it doesn't make it any easier to watch as she says goodbye to her found family in Seattle, especially Meredith, who has lost so much and is now losing her "person," too. On the bright side, Cristina and Meredith are still close as we often see Meredith texting her after her exit.

Let's talk about one of the most controversial exits in Grey's history, shall we? When actor Justin Chambers left the show suddenly, Alex had to leave too, but how? He disappeared after rallying Meredith's supporters for her licensing hearing, and eventually sent letters explaining why. While searching for supporters for Meredith, he tracked down Izzie, and he found out that she had their children with the eggs they'd frozen during Izzie's cancer battle. Alex then leaves his friends and his career — not to mention his wife Jo — to get back together with Izzie. While it's not a tragedy in the sense of killing off a character, it wasn't easy for many viewers to see Alex's character end this way after nearly 15 years of character development.

Can there really be any No. 1 on this list other than Derek Shepherd? From the beginning, he was basically the show's leading man, as Meredith's true love. They eventually get together for good, get married, and have children, despite their struggles with conflicting career goals. Then, in season 11, Derek gets into a shocking car accident. Due to the poor quality of care he receives at the hospital where he's taken, the extent of his injuries isn't found until it's too late, and he is put on life support until Meredith arrives, tells him he can go, and turns off his machines.

Even years later, it's impossible to forget the effect this tragedy has had on the show, especially considering Derek's still in Meredith's heart all these years later. When she contracts COVID-19 in season 17, she has visions of Derek on a beach as she slips in and out of consciousness. While on the beach, They discuss their life together, have a wedding on the beach, and embrace before Meredith returns to the real world and her children who need her, leaving Derek alone on the beach walking into the sunset. While the reunion offered some level of closure, it was nonetheless devastating to watch Derek slip away once more.