This article contains spoilers for Grey's AnatomyGrey's Anatomy has been running since 2005 and has an astounding 19 seasons, making it the longest-running scripted primetime show on ABC. Without fail, this drama has created hundreds of love triangles, plot twists, patient/doctor relationships, and incurable cases, and it doesn't get old. With such a long-running show about a hospital, clearly there are going to be some major deaths, even ones including main characters. That being said, here's a list of the most impactful deaths that have been featured on this never-ending show.
7 Ellis Grey
Ellis Grey was an intense character in this drama series, proving to be memorable in every episode she showed up in. As the mother of Meredith, it's proven time and time again that she is the reason for most of the problems that pop up in Meredith's life. Ellis didn't give her child the best upbringing, had affairs, and eventually was diagnosed with Alzheimer's Disease. Times Mojo states that Ellis was no-nonsense and a god among surgeons, so it was tragic yet right that she had a heart attack at the end of season three.
6 Denny Duquette
Denny Duquette (Jeffrey Dean Morgan) was the most memorable love interest for Izzie Stevens, and also the love interest to several individuals watching every Thursday night. ScreenRant states that Denny was a heart patient that was waiting for a transplant, but after being under Izzie's care, the two fell in love and had a heartbreaking romance. Denny was charming, memorable, witty, and the perfect match for Izzie, but it wasn't in the cards for them to be together in the long run. Izzie ended up cutting his LVAD wire in order to make his heart look worse than it actually was, so he would be bumped up on the transplant list, but it backfired incredibly on them. Denny died just hours after receiving the transplant, and Izzie had to live with the choice she made.
5 Andrew Deluca
Deluca was a fresh face that first appeared in season 11, eventually becoming a love interest for Meredith before he falls to the hands of a family illness and is diagnosed with bipolar disorder. During the time that he was a recurring character on the show, he went through a lot; such as an almost life-ending beating given to him by Alex Karev, due to a misunderstanding. In his final episodes, things start to get sad for Deluca, as his friends and co-workers keep him at arms length once confirming his diagnosis, not believing him when he found out about a human trafficking issue regarding a patient. Deluca is stabbed by an unknown individual, but was linked to him being right about the trafficking, making his death that much worse.
4 Lexie Grey
Lexie was the half-sister of Meredith and at first, wasn't well received by the majority of the hospital. However, she eventually gets to be in good graces with the doctors and works her way up the ranks alongside her friends and colleagues. In season nine, a handful of surgeons were on a small plane coming back from a difficult surgery, and among them, was Lexie. Everyone was badly injured, including Arizona, who had to get her leg amputated, as well as Derek, whose hand was never the same once they were rescued. Lexie, however, was trapped under a huge piece of plane, and was bleeding out, helpless as she remained there with Mark by her side. Mark tried to make the best of it, promising that they were going to get rescued and have the life that both of them dreamed of. Lexie died shortly after they made their promises to each other.
3 Mark Sloan
Following the events of the plane crash, fans were shocked when Mark Sloan (Eric Dane) died a few episodes later, adding to the grief they were already experiencing from the loss of Lexie. His daughter, Sofia, was still a baby, and Callie begged with him to stay alive, but the complications were too great, and he didn't survive more than a few days. Grey's Anatomy did in fact play a cruel trick on viewers and gave them false hope that Mark was going to survive after Derek claimed it was a miracle, and he would live... only to kill him off that same episode.
2 Derek Shepard
In his prime, Derek was the blue-print for husband material due to how much he loved Meredith, his children, and his career. Of course, he had to have a fatal flaw, and in the end, had several, but there was a time when everyone loved Derek. Despite the fact that he originally cheated on his first wife with Meredith, many people considered them to be the perfect couple... even soulmates. So that's why it was so tragic when he died by getting hit by a car, and to make matters even worse, him and Meredith weren't on the best of terms before he died. He had three children, a huge family, including his sister Amelia, and of course, Meredith.
1 George O'Malley
From the start, George was the original nice guy. Hopelessly in love with Meredith and the art of saving people, George often came off as needy and slightly annoying. But to the root of it, he was a great character. He was there for Bailey when she had her son, literally helping birth him while she was panicking and alone. He was there for Izzie when Denny died. He was always there for his friends, even Christina, who often made fun of him and bullied him. When a patient came in with an antisemitic tattoo on his body, George delivered the perfect monologue about how he's a terrible person, and yet he's still receiving treatment because that's what doctors do. To this day, fans still have big reactions to Meredith finding out that it's George who's the John Doe, his finger writing 007 on her palm.