The first season introduces the main character, Meredith Grey, as she enrolls in Seattle Grace Hospital's internship program and faces unexpected challenges and surprises.

The series' protagonist and title character is Dr. Meredith Grey (Ellen Pompeo), who is accepted into the residency program at the fictional Seattle Grace Hospital.

She joins the program as an intern and is assigned to work under their resident Dr. Miranda Bailey (Chandra Wilson), along with fellow interns: the extremely competitive Dr. Cristina Yang (Sandra Oh), the insecure Dr. George O'Malley (T. R. Knight), ex-model Dr. Izzie Stevens (Katherine Heigl), and the arrogant Dr. Alex Karev (Justin Chambers).

Meredith is in a romantic relationship with her attending Derek Shepherd (Patrick Dempsey) a stranger she had a one-night stand with, and is the daughter of the renowned surgeon Ellis Grey (Kate Burton), who now suffers from Alzheimer's.

The series was chosen in the top 10 for several 2005 "best of television" lists, including USA Today, San Jose Mercury News, The New York Times, The Boston Globe and Chicago Tribune.

The staff writers were Rhimes, Parriott, Ann Hamilton, Vernoff, Kip Koenig, Mimi Schmir, Gabrielle Stanton, and Harry Werksman, Jr.

John David Coles, Scott Brazil, Darnell Martin, Sarah Pia Anderson, and Wendey Stanzler.

[14][15] It was originally scheduled to run in the Boston Legal time slot for just four weeks, but after receiving high ratings remained in the time-slot for the remainder of the season.

[16] ABC Entertainment President Steve McPherson commented on the scheduling decision: "Ultimately we decided that, without having adequate lead time or marketing dollars to devote to moving either show so late in the season, we'd continue to let Grey's build on its tremendous momentum through May".

[20] Determined not to have a show in which "all the extras are white, except the lone janitor", she has created what The New York Times has called "one of the most colorful backgrounds in television.

The interns are mentored by their resident Miranda Bailey portrayed by Chandra Wilson, a disciplined woman who is nicknamed "The Nazi".

[24] Commenting on the first season's high ratings, Magna Global USA media analyst Steve Sternberg stated: "Roughly 80 percent of households during primetime only have one TV set on.

In regard to the first season, New York Daily News named Grey's Anatomy a "winner",[26] whereas Newsday expressed a positive opinion by stating "You simply can't stop watching!

"[26] Walter Chaw from Film Freak Central said the show was "so odious, so repugnant, that it's impossible not to have predicted its newly-minted role as the most popular program in the land.

"[27] The Washington Post's Tom Shales was critical of the early series, finding it reminiscent of ER and commenting that: "The show is much more a matter of commercial calculation than an honest attempt to try something fresh and different."

He called Rhimes' script for the pilot episode "nothing but a casserole made of equal parts ham-and-corn", writing that overall: "It's a 'new' show only in the sense that Dr. Frankenstein's monster was a new man.

"[28] Kate Aurthur for The New York Times deemed the show a hybrid of Ally McBeal, Sex and the City and ER, writing of the news that it had become the highest-rated midseason drama in 12 years that: "When you parse its ratings, Grey's Anatomy underscores one of the real lessons of the current season - men will watch shows with a female lead.

"[30] HomeTheaterInfo.com, however, had a mixed perspectives on the pilot, noting that the storylines were similar to fellow ABC series Desperate Housewives, but also "brilliantly written, extremely well-acted and directed to near perfection.

"[31] IGN gave a positive review stating, "The show isn't derivative, and actually maintains a tenuous edge over its predecessor, the characters resemble real people - who are fragile, and yes, fallible."

"[32] Sandra Oh won Best Supporting Actress – Series, Miniseries or Television Film at the 63rd Golden Globe Awards[21] and Outstanding Performance by a Female Actor in a Drama Series at the 12th Screen Actors Guild Awards in 2005,[33] for her portrayal of Cristina Yang during Grey's Anatomy's first season.

Under the title Grey's Anatomy: Season One, the box set consists of episodes with Dolby Digital 5.1 surround sound and widescreen format.