Throughout its lengthy run, Greys Anatomy has said goodbye and then hello again to countless popular characters.

As the first series regular to exit from the ABC medical drama, fans were surprised when Isaiah Washington (Preston Burke) returned to Greys Anatomy in 2014 seven years after he was fired for using a homophobic slur during a fight with Patrick Dempsey.

Hes a prepared, energized actor and he was ready to play. I will say, though, he was nervous, creator Shonda Rhimes told Entertainment Weekly about his season 10 return, which served as a way to wrap up Sandra Oh (Cristina Yang)s story line. My first decision and my first responsibility is to the story, she said. I have to be the keeper of the story and make sure that were telling the story we need to tell, regardless of whatever outside factors are involved or whatever history is involved and, frankly, Sandra was so lovely and open to it. It has been a really kind of amazing experience.

The producer added at the time that Isaiah is a person that we all love and have loved for a very long time.

I feel like there have been a lot of people that have been like, How can you do this? Rhimes continued. And I feel very strongly and fully believe in peoples ability to grow and change and learn from their mistakes and when they know better, to do better. If people dont think that, over the course of seven years, its possible for a human being to change, then there really is no future for the human race at all.

While several actors and actresses left Grey Sloan following Washingtons departure, Dempseys exit (and the death of his character, Dr. Derek Shepherd) rocked the fanbase in 2015. Viewers were delighted, however, when he appeared in several season 17 episodes through Meredith (Ellen Pompeo)s dreams as she battled coronavirus.

Theres just so much darkness, and we knew that coming together would be a little ray of light, Pompeo told Deadline about reuniting with her former onscreen husband in 2020. And so, I think we had the same idea, at the core, to want to help people and bring a smile to peoples faces. So, he loved the idea, and we were just so excited, and we had a ball filming it. It was very healing to come back, and know that were doing something good, putting out a positive story, a healing story, going to make people smile, and I think, for me, Im really grateful for the opportunity to be able to be at this place in the show where we can do this.

The following season, viewers were in for another surprise when Scott Speedman, who appeared on a season 14 episode as Dr. Nick Marsh, ran into Meredith in Minnesota. After the episode aired in September 2021, news broke that the Felicity alum would be a series regular for season 18.

It is timing. To be totally honest, the last time wasnt the right time. I havent done a show since the last show I did. I think a lot of people love that schedule, and I really do, too, but I was wanting to do other things, the actor told Deadline about joining the cast four years after his initial guest star role. But you always know, you put something in the back of your mind when you do have chemistry with somebody, and you do enjoy the work experience, because thats rare, actually. So, when this opportunity came around, I was trying to think of why not to do it, and I couldnt come up with any reasons. It was a great show, really fun people, and it just felt the right timing for me. I wanted to jump in, and then, when I heard what the storyline could be, that was exciting to me.

Greys Anatomy airs on ABC Thursdays at 9 p.m. ET. Scroll through for more on the biggest returns over the years:

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Biggest Greys Anatomy Returns Over the Years - Us Weekly