While listening to countless angry messages left on her machine, Samantha ponders about one truthful fact: "Everyone hated me, except for one friend from high school and, for some reason, my boyfriend." Until she receives her bridesmaid dress for a wedding she cannot remember, on account of her recovering from amnesia.
Samantha attends the wedding to know who actually liked her enough to make her bridesmaid. But before the ceremony even started, she meets the bride at the hallway and she wasn't too pleased Sam was there. Turns out, Sam had started a wedding pool to bet on how long the marriage will last and in the process, she got herself uninvited from the wedding. Only of course, she couldn't remember all those details.
So Sam tries to make peace with the bride, who happens to be moneyed and influential. While trying to be back in her circle, she inadvertently ditches her high school chum, Dena, for them. In the end, Sam realizes (via a flashback she conveniently remembers) these "friends" of hers are horrible people and tries to woo back the only friend who actually likes her (Dena).
Also present at the wedding was Sam's boyfriend, who she broke up with after her accident/amnesia, after realizing she wasn't treating him right. Boyfriend Todd is played by Barry Watson (Seventh Heaven), and it looks like he is starting to see the changes in Samantha. Will they get back together?
Samantha Who? is probably the surprise hit of the season. And other than Christina Applegate's perfect comedic timing, also equally delightful to watch is Jean Smarts, who plays her mother and Jennifer Esposito, who plays her other friend.