The character Alex Karev was not in the original pilot script. His role was inserted into the pilot as an afterthought, in order to provide a foil, as well as male companionship for Dr. George O'Malley. Since he wasn't added until after the pilot was shot, scenes with him were either re-shoots or digitally altered.
Ellen Pompeo has stated in an interview that Shonda Rhimes originally wanted to pair up her character with Isaiah Washington's because she wanted an interracial couple on the show. However, Pompeo preferred Patrick Dempsey, because in real-life, she is in an interracial relationship, and thus being paired up with Washington felt too close to home.
Shonda Rhimes said on an interview that she had a clear idea for the show's end, but its success kept growing to the point that her ending was no longer proper, so she decided to use the idea on a storyline and come up with another ending.
As is common for major television and film productions, stars of the show have become famous in roles other than those they originally sought. Sandra Oh was initially looking to audition for the part of Dr. Bailey. On The Oprah Winfrey Show (1984), Isaiah Washington (Dr. Burke) said that he had auditioned to play the role of Dr. Shepherd.
In an early episode, Meredith is seen posting a poster asking for a roommate. The poster is only visible for a second, but it mentions that "Bush supporters need not apply" along with other details about the house.
Similarities between Katherine Heigl's characters in Roswell (1999) and Grey's Anatomy (2005): in each, her character, Isabel/Isobel, has a pivotal scene in a pink, strapless gown, has a love interest named Alex, sees, talks to, and dances with a dead lover.
The first person to refer to Dr. Sloan as "McSteamy" was Meredith. However, Meredith was not the first character in the show to use the term "McSteamy" in general. Nurse Tyler was the first to say it, instead of "McDreamy", as he most likely misheard.
The producers of Grey's Anatomy (2005) released a novel in 2006 depicting the lives and happenings of two bit-part characters; Joe the Bartender and Nurse Debbie. The book is double-sided, written in blog and IM form, while gossiping on the actions of the Grey's characters. The events discussed, give background information for Joe and Debbie themselves, and give insight on the events and cases the doctors deal with on the show.
An article in a 2014 issue of the scholarly journal Communication Research reported on the results of several studies that all found that being a regular viewer of Grey's Anatomy (2005) correlated with having much more strongly negative attitudes toward organ donation than non-viewers. The article said, in part: "Of the medical dramas examined for depicting organ donation myths, perhaps no program features as many inaccuracies as Grey's Anatomy (2005) (see Morgan et al., 2007; Morgan et al., 2010; Morgan, Movius, & Cody, 2009; Quick, 2009). Unfortunately, the impact of these inaccurate media portrayals results in misguided societal beliefs about organ donation (Morgan et al., 2010) and often surface as reasons for declining to register to be organ donors (Morgan et al., 2005)."
The Inuit doll that frequently appears in episodes, is named Ipecac. Ipecac is featured in an Easter Egg in the Season One DVD Bonus Features, where the cast and crew discuss the doll, its name, origins, and a plot to kidnap it.
My So-Called Life (1994), whose protagonist was named Angela Chase, was an ABC show, just like Grey's Anatomy (2005). Three of the stars of My So-Called Life (1994) have made memorable appearances on Grey's Anatomy (2005): Wilson Cruz played a gay teen, who was one of Angela's best friends, Ricky Vasquez made a guest appearance as Kyle, a gay man in 2011; Tom Irwin, who starred as Angela's father, Graham Chase, appeared three times as Police Commander Marty Hancock, who assisted Seattle Grace during one of its most crucial crises in 2010/11; and, Jeff Perry, who played Angela's teacher, Richard Katimski, was featured as Thatcher Grey, the father of Meredith, from 2006-2011.
All of the original series cast (exc. Justin Chambers and James Pickens Jr.) received at least one nomination for a major award. Most of them even won their category, including Chandra Wilson (SAG), Sandra Oh (SAG, Golden Globe), and Katherine Heigl (Emmy).
Eric Dane (Dr. Mark Sloan) decided to leave the show. Shonda had a hard time deciding what to do with his character, so she decided the best option was for him to die. In an interview, she had stated that she did not want Mark to be mourning the loss of Lexie, and that they're still together somehow.
Meredith's dreams in the first episode of season five can be considered a foreshadowing of Derek's death in season eleven, since both events involve Derek's car being rammed by a much larger vehicle (a bus in season five, and a truck in season eleven). Also, when Meredith creates a giant blueprint of candles on Derek's land, he says "Stay here. Wait for me." These words are also the last words he told Meredith before leaving for a flight to D.C.
T.R. Knight left the show at the end of season five, because he felt that his character George O'Malley wasn't given enough storyline, or on-screen time throughout the season. He said that there was a "breakdown in communication" between him and Creator Shonda Rhimes. Instead of making any demands, he just asked to be written out of the show.
All of the original interns (Meredith Grey, Cristina Yang, Alex Karev, George O'Malley, and Isobel Stevens) have had surgery at some point in the series. Meredith for liver donation to her father, an appendectomy, the surgeries to save her life after being attached by a patient, and a c-section, Christina for an ectopic pregnancy, Alex for the gunshot, George after he got hit by a bus, and Isobel for her cancer, as well as a transplant surgery for her daughter's cancer.
In the hospital shooting episode, when Meredith tells Cristina she is going to be a godmother, Cristina says if they get into a plane crash, she will keep the child, and at the end of season eight, Meredith, Derek, and Christina are all in a plane crash.
Sarah Drew and Jesse Williams knew that Jackson was going to interrupt April's wedding to Matthew, when they began filming season ten, so when they read it, in the table read for season ten episode twelve, they weren't that shocked.