Maggie (Cameron Diaz) and Rose Feller (Toni Collette) are sisters with nothing in common but their shoe size. They were raised by their father Michael (Ken Howard) and stepmother (Candice Azzara) after their mother died in a car accident. Rose is the eldest; a plain and serious lawyer who is protective of Maggie despite her flaws. Maggie is a free spirit who is unable to hold a steady job (due to her virtual inability to read) and turns to alcohol and men for emotional and financial support. Rose grudgingly allows Maggie to move in with her in her Rittenhouse Square, Philadelphia apartment when their stepmother throws her out of the house. Their already difficult relationship ends, however when Rose catches Maggie in bed with Jim (Richard Burgi), her boyfriend. Maggie subsequently disappears from Rose's life.
A few days before, while secretly looking through her father's desk for money, Maggie discovers a bundle of old greeting cards containing cash. She is astonished to discover that the cards are addressed to both her and Rose and are from their grandmother Ella (Shirley MacLaine). Now, homeless and without job prospects, Maggie travels to Delray Beach, Florida to find her and hopefully a new source of income.
When Ella first hears from Maggie, she invites her to stay in her home, partially out of guilt for abandoning her responsibilities as a grandmother. However, as time passes, Ella discovers that Maggie has come to do nothing but sunbathe and take money from her. Maggie asks Ella to finance an acting career for her; Ella agrees to match her salary dollar-for-dollar if she accepts a job with the assisted living section of her grandmother's retirement community. Meanwhile, Rose has decided to quit her job, become a dog-walker, and date Simon Stein (Mark Feuerstein) whom she had previously ignored. They become engaged.
Maggie befriends one of her patients, a blind retired professor of English literature (Norman Lloyd), who has asked Maggie to read works of poetry to him. She does so, but with great difficulty. After asking if she is dyslexic, the professor encourages Maggie to continue reading to him while offering emotional support to her. Maggie finds a friend in the professor, the first person in her life who does not ridicule her difficulties with reading (and actually helps her to improve in this area). As time passes with the professor, Maggie's confidence grows not only with reading but with her general image of herself. In addition, she also becomes friendly with the residents of the retirement community. In doing so, Maggie discovers a livelihood that is greatly needed among the elderly women: a personal clothing shopper, an activity for which Maggie shows enormous talent. Ella (who also does not ridicule her difficulties with math) offers to run the financial aspects of the business. In the process, they become close and resolve their past history.
Ella has also secretly contacted Rose and sends a plane ticket asking her to come for a visit. Rose is excited to hear from her long-lost grandmother, but her pleasure quickly sours when she arrives and discovers that her sister already lives there. Long conversations with Ella reveal that their mother's car accident was an act of suicide (their mother struggled with a mental disorder and refused to take her medication). Ella never recovered from her death and never resolved her feelings towards her granddaughters, whom she felt contributed to her daughter's difficulties. The three women bond and learn to resolve their complicated past. At Rose's wedding, Ella also reconciles with Michael and Maggie reads a poem to Rose as a wedding gift.