Meredith, Lexie and Callie treat a man who was accidentally run over by his pregnant wife and simultaneously try to keep her calm so that the baby isn't affected.

Addison, Meredith and Alex become concerned with Derek when he plans to take extreme measures in order to save a patient's life.

The season was produced by Touchstone Television ABC Studios, The Mark Gordon Company, ShondaLand, and was distributed by Buena Vista International, Inc.

Ellen Pompeo continued her role as protagonist and narrator of the series, Dr. Meredith Grey, a resident physician and a surgeon.

Katherine Heigl portrayed resident Dr. Isobel "Izzie" Stevens whose previous relationship with the now-deceased patient Denny Duquette threatens her career once again.

Eric Dane's character, plastic surgeon Dr. Mark Sloan, begins a relationship with intern Dr. Lexie Grey, Meredith's half-sister portrayed by Chyler Leigh.

Brooke Smith appeared in 7 episodes as cardiothoracic surgeon Dr. Erica Hahn, Callie's love-interest, who eventually resigns and moves away.

Patrick Dempsey portrayed neurosurgeon Dr. Derek Shepherd whose relationship with Meredith Grey is the series' main storyline.

Originally only signed onto the show until December 2008,[25] it was later announced Kevin McKidd would be promoted to regular status after his fifth episode on the series aired.

[26] Shonda Rhimes said, "I am excited to have Kevin McKidd joining us for the season, he's been a delight to collaborate with and brings incredible passion, talent and creativity to his work.

"[27] Weeks after Hunt's first appearance on the show, Matt Roush of TVGuide comments that "Hunt/McKidd is the most encouraging thing to happen to Grey's Anatomy in quite a while."

Robert Rorke of the New York Post states that McKidd was brought in as Hunt to "boost the sagging fortunes" of the show's ratings.

"[28] Numerous supporting characters have been given expansive and recurring appearances in the progressive storyline, including: Melissa George as Sadie Harris, Kimberly Elise as Dr. Jo Swender, Jessica Capshaw as Dr. Arizona Robbins, Amy Madigan as Dr. Wyatt, Mary McDonnell as Dr. Virginia Dixon, Eric Stoltz as William Dunn,[29] Jennifer Westfeldt as Jen Harmon, Ben Shenkman as Rob Harmon, Shannon Lucio as Amanda and Samantha Mathis as Melinda.

Jeffrey Dean Morgan returned as the deceased Denny Duquette in Izzie's hallucinations due to a brain tumor.

Former series-regular Kate Walsh also returned as Dr. Addison Montgomery for two episodes ("Before and After", "An Honest Mistake") as part of a four-part crossover with her spin-off series, Private Practice.

Her fellow cast member Audra McDonald reprises the role of Naomi Bennett from the third season two-parter "The Other Side of This Life", which functioned as a backdoor pilot for the spin-off.

Tyne Daly joined the series in the role of Carolyn Shepherd (née Maloney), Derek's mother in the episode "Sympathy for the Devil".

"[30] Robert Bianco from USA Today said "Happily, it now seems to have landed on solid ground, with its best ensemble and most-engaging stories in years" regarding the show's fifth season.

The return of Izzie's deceased fiancé Denny and the resumption of their romance during the season also proved unpopular with fans,[31] and was deemed "the world's worst storyline" by Mary McNamara of the Los Angeles Times.

[32] The episode in which Izzie married long-term love Alex received 15.3 million viewers, the largest television audience of the night.

Otis Brawley, chief medical officer at the American Cancer Society, commented that Izzie's treatment options were unrealistic.

"[35] Chandra Wilson won the 2009 NAACP Outstanding Actress in a Drama Series for her portrayal of Dr. Miranda Bailey during the season.

For the U.S & Canada, a special limited box set edition of the season was released exclusively for Target Stores, this box set included an extra disc with over 100 minutes of additional bonus content, including more unaired scenes of the season and crossover episodes with the Grey's Spin-Off, Private Practice.

[37] With this release, an exclusive extended version of the episode "Elevator Love Letter" was included among the rest of the special features.