Actors Ellen Pompeo, Sandra Oh, Katherine Heigl, Justin Chambers, and T. R. Knight reprised their roles as surgical interns Meredith Grey, Cristina Yang, Izzie Stevens, Alex Karev, and George O'Malley respectively.

Previous main cast members Chandra Wilson, James Pickens, Jr., Isaiah Washington and Patrick Dempsey also returned, while Kate Walsh, who began the season in a recurring capacity, was promoted to series-regular status, after appearing in 7 episodes as a guest-star.

Also heavily developed was the storyline involving Izzie Stevens' relationship with patient Denny Duquette, which resulted in high critical acclaim and positive fan response.

The series was chosen in the top 10 for several 2006 "best of television" lists, including USA Today, San Jose Mercury News, TV Guide, and Orlando Sentinel.

Among the other directors are Wendey Stanzler, Mark Tinker, Jeff Melman, Jessica Yu, Lesli Linka Glatter, Michael Dinner, Dan Minahan, David Paymer, Julie Anne Robinson, Tricia Brock, and Seith Mann.

Danny Lux continued his position as the main music composer for the series, while Herbert Davis, Tim Suhrstedt and Adam Kane served as the season's cinematography directors.

After the departure of Laurence Bennett, the production design team was taken over by Donald Lee Harris, with Amy B. Ancona and Brandee Dell'Aringa joining for 10 episodes each.

"[45] Series creator Shonda Rhimes discussed costuming choices in the scene which saw the interns gather around Denny's deathbed, explaining: "Meredith and Cristina and Alex and George and Callie are all dressed, not for a prom, but for a funeral.

"[46] Peter Horton, expressed that his plan of developing Chandra Wilson's character, Miranda Bailey, was to focus on the similarities between her and the actress, noting that "there's not a mean bone in her body, but she's solid and steady, like a rock.

"[47] Fellow cast member James Pickens, Jr. described Wilson's portrayal of Miranda Bailey as "a breath of fresh air, literally and figuratively", also noting how the force she delivers is mainly due to the start of her career being in theater.

[47] He stated that the plot of the episodes had to "fill the demands of the Super Bowl", which was scheduled to air in the same night: "We really wanted something different and Shonda [Rhimes] came up with the idea of this bomb, that we found simply outstanding!"

Ellen Pompeo acted as Meredith Grey, the protagonist and the narrator of the series, a surgical intern who struggles to balance the difficulties of the competitive career she has chosen, with her troubled personal background.

Chandra Wilson portrayed surgical resident and brilliant general surgeon Miranda Bailey, the mentor of the five interns, whose rudeness and cold attitude earns her the nickname "The Nazi.

"[48] James Pickens, Jr. portrayed Seattle Grace Hospital's Chief of Surgery, Richard Webber, whose relationship with Meredith Grey's mother, which occurred 21 years ago, threatens to ruin his marriage.

[48] Isaiah Washington played the role of attending physician and cardiothoracic surgeon Preston Burke, who learns that Cristina, with whom he had a sexual relationship, is pregnant with his child.

Patrick Dempsey portrayed attending neurosurgeon Derek Shepherd, whose relationship with intern Meredith Grey has been the focal point of the series since its inception.

Although originally conceived as a guest-star with a 5-episode story arc,[49] Kate Walsh decided to extend her contract following positive reviews from critics and fans, resulting in her getting promoted to series-regular status.

Sara Ramirez appeared in a 9-episode arc in the season, portraying orthopedic surgical resident Callie Torres, introduced and developed as a love-interest for the character of George O'Malley.

Renowned surgeon Ellis Grey, Meredith's mother, who is suffering from Alzheimer's disease, continues her recurring role from the first season, being portrayed by Kate Burton.

Brooke Smith portrayed Erica Hahn, a cardiothoracic surgeon at Seattle Presbyterian Hospital, who is revealed to have been a rival of Preston Burke ever since they attended medical school together.

[50] Jeffrey Dean Morgan appears in 6 episodes throughout the season, portraying patient Denny Duquette, who begins a relationship with Izzie Stevens, but ultimately dies following an unsuccessful heart transplant surgery.

Eric Dane, who would be promoted to a series-regular in the third season,[40] appeared in the eighteenth episode, portraying attending physician, otolaryngologist and plastic surgeon Mark Sloan, Addison Montgomery's former lover, whose affair with her is presented as the reason behind the estrangement of her husband, Derek Shepherd.

[58] He noted that the ensemble, composed of "countless comely females and enough strong, competitive males" remains outstanding in primetime, being iconic, due to the vast interpretations regarding the main cast.

[58] In response to the bomb story-arc, he called the 2 episodes "juicy", while assessing that they "followed a storyline that not only explained the series up to that point, but featured all of the characters in their more-or-less purest from."

[58] He also expressed excitement in the doors opened by the previous season's cliffhanger, seeing the arrival of Montgomery (Walsh) as "certainly speaking to the show's focus on relationships over the nuts-and-bolts of being a surgeon", while praising Rhimes for continuing to "merge those disparate elements in the way that does, or at least should be a source of enthusiasm for both men and women, creating an atmosphere both professional and intimately personal, often at the same time."

Gilchrist stated in response to Stevens' development in the last part of the second season: "Izzie's descent into abject hysteria, which followed her season-long sanctimoniousness about everything, actually made me want something terrible to happen to her too.

"[60] Regarding the second season, Kevin Carr from 7M Pictures said "Rhimes really just put Scrubs, E.R., Sex and the City and even a dash of The Love Boat in a blender and poured out Grey's Anatomy.

The sixteenth and seventeenth episodes of the season secured writer Shonda Rhimes a nomination for the Primetime Emmy Award for Outstanding Writing for a Drama Series in 2006.

Under the title Grey's Anatomy: The Complete Second Season – Uncut, the box-set consists of episodes with Dolby Digital 5.1 surround sound and widescreen format.

For Target Stores in the United States, the season was released with a bonus disc attached that included a special interview with the cast and crew at the PaleyFest 2006 and some extra deleted scenes.