Good in Bed, Jennifer Weiner's debut novel, features Cannie Shapiro, a twenty-eight-year-old writer in Philadelphia. Cannie is a typical twenty-something in her desire to lose weight, her frustration with her job, and her quest for love. Cannie is smart, sassy, and wickedly funny. She has a very supportive, if off-beat, family, great friends, and a loyal dog named Nifkin.

The book opens with Cannie reading a column in a national women's magazine entitled, "Good in Bed". The article is entitled "Loving a Larger Woman" and is written by Cannie's ex-boyfriend, Bruce. Although the woman is only referred to as C, Cannie quickly realizes that the article is about her. Cannie is humiliated and immediately enrolls in a weight loss program, where she meets a kind doctor whom she calls Dr. K.

Cannie's self esteem takes a nosedive and she begins to feel like Bruce might be her only chance at love, so she tries desperately to win him back, yet to no avail. When his father unexpectedly dies, Bruce turns to Cannie for comfort and they end up having sex, which results in Cannie getting pregnant. Bruce gets a new girlfriend, and Cannie's life becomes a wild ride. She meets and befriends a famous actress, sells a screenplay to a big Hollywood studio, and unexpectedly finds her father, whom she has not seen or spoken to in several years.

When Cannie has an accident and prematurely delivers her baby, whose health is then questionable, she realizes that there is more to life than being thin. Worrying about the well-being of her premature daughter, Cannie cannot eat and spends her days walking around the city. She ends up achieving the body she always wanted, only to discover that there are other things in life that are much more important.

Cannie's baby lives, Dr. K and Cannie fall in love, and Cannie finally accepts herself as she is, body and all. She ends up publishing an article entitled "Loving a Larger Woman" in the same national magazine which originally ran Bruce's article. The book ends with Cannie accepting herself, her body, and her family, and well on her way to living happily ever after.