The show centered on Samantha Newly (Christina Applegate), a vice president of a real estate firm who develops retrograde amnesia after a hit and run accident.

After awakening, she progressively realizes to her dismay that she had been selfish and unlikable before her accident, and therefore sets out to make amends and become a better daughter to her somewhat dysfunctional parents, Howard (Kevin Dunn) and Regina (Jean Smart), a better friend to self-centered Andrea (Jennifer Esposito) and needy but well-meaning Dena (Melissa McCarthy), and a better on-again, off-again girlfriend to her roommate and ex-boyfriend, Todd (Barry Watson).

[1] Produced by ABC Studios, Donald Todd Productions, and Brillstein-Grey Television, the series was officially greenlit and given a thirteen-episode order on May 11, 2007.

[2] The show was originally named Sam I Am until ABC renamed it Samantha Be Good due to conflicts with the estate of Dr.

[5] Early television promotions for the series, playing off of the concept of its lead character's amnesia, appeared without stating any specific title.

The lack of stated title (with a question mark shown instead) was attributed in promotions to Applegate's character not remembering the name of the series.

[10] The series, which was filmed in the single-camera format, went on hiatus during the 2008–2009 television season and returned in a new timeslot on Thursday, March 26, 2009, following In the Motherhood before being pulled.

Without a strong lead-in (provided by Dancing with the Stars in its first season) and paired with another failing ABC comedy In the Motherhood, the ratings for Samantha Who?

Its competition shifted from The Game to Girlfriends on The CW and from Rules of Engagement to Two and a Half Men on CBS.

Walt Disney Studios Home Entertainment released the entire series on DVD in Region 1.

On February 9, 2012, it was announced that Lionsgate Home Entertainment had acquired the rights to the series and plan on re-releasing it.