Jackie (Susan Sarandon) and Luke Harrison (Ed Harris) are a divorced New York City couple struggling to help their children Anna (Jena Malone) and Ben (Liam Aiken) be happy with this sudden change of lifestyle. Luke, an attorney, is living with his new girlfriend, Isabel Kelly (Julia Roberts), a successful fashion photographer several years his junior. Isabel tries hard to make Anna and Ben feel comfortable and happy with her, but Anna repeatedly rejects her overtures while Ben, who is generally kind to Isabel, adds extra complication with his mischievous nature. Isabel behaves with contempt tempered by caution around Jackie, believing she overcompensates for her divorce by spoiling her children.
Jackie, a former publisher turned stay-at-home mom, gives Isabel a cold reception, seeing her as an overly ambitious career woman. She also continues to harbor malice towards Luke, as seen in a confrontation about Isabel. After a long string of arguments and hurt feelings involving Isabel, Jackie, and Anna, Luke proposes to Isabel, making her Anna and Ben's soon-to-be official stepmother. This causes even more friction. Jackie is diagnosed with lymphoma, which is discovered to be terminal. She experiences a range of negative emotions, angry at the woman who she feels was responsible for breaking up her family, and angry that after all of the sacrifices she made for her family, she will never see her children grow up. Jackie actively sabotages Isabel's effort to bond with the children even to the point of refusing to allow her to take Anna to see a rock band that she likes and then taking her to the same concert a few weeks later herself.