It is Valentine’s Day and florist Reed Bennett (Ashton Kutcher) proposes to his girlfriend Morley Clarkson (Jessica Alba), who accepts. Reed’s closest friends, Alfonso Rodriguez (George Lopez) and Julia Fitzpatrick (Jennifer Garner), aren’t surprised when Morley changes her mind and leaves Reed the same day. On an airplane to Los Angeles, Kate Hazeltine (Julia Roberts), a captain in the U.S. Army on a one-day leave, befriends Holden Wilson (Bradley Cooper). When the plane lands and Kate has to wait hours for the taxi, Holden offers his limousine, which Kate accepts.
Julia, an elementary school teacher, has fallen in love with Dr. Harrison Copeland (Patrick Dempsey), but does not know that he is married to Pamela (Katherine LaNasa). Harrison tells her that he needs to go to San Francisco for a business trip. Wanting to surprise him, Julia also flies to San Francisco, despite Reed’s warnings. Julia finds out that he is married and gets the name of the restaurant where he and his wife will be dining that evening. The restaurant’s owner allows her to dress as a waitress, and Julia makes a scene at the restaurant, making Pamela suspicious. One of Julia’s students, Edison (Bryce Robinson), orders flowers from Reed, to be sent to his teacher. Julia suggests to Edison to give the flowers to a girl named Rani in his class who has a crush on him.
Edison’s babysitter Grace Smart (Emma Roberts) is planning to lose her virginity to her boyfriend Alex Franklin (Carter Jenkins). The planned encounter goes awry when Grace’s mother discovers a naked Alex in Grace’s room, rehearsing a song he wrote for Grace. Edison’s grandparents, Edgar (Héctor Elizondo) and Estelle Paddington (Shirley MacLaine) are facing the troubles of a long marriage. Estelle admits to Edgar about an affair she had with one of his business partners. Although she is deeply sorry, Edgar is very upset. Grace’s high school friends, Willy Harrington (Taylor Lautner) and Felicia Miller (Taylor Swift), are experiencing the freshness of new love, and have agreed to wait to have sex.
Sean Jackson (Eric Dane), a closeted gay professional football player, is contemplating the end of his career with his publicist Kara Monahan (Jessica Biel) and his agent Paula Thomas (Queen Latifah). Kara is organizing her annual “I Hate Valentine’s Day” party, but becomes interested in sports reporter Kelvin Moore (Jamie Foxx), who was ordered to do a Valentine’s Day report by his boss Susan Moralez (Kathy Bates), and who shares Kara’s hatred of the holiday. Paula has hired a new receptionist named Liz Curran (Anne Hathaway), who dates mail-room clerk Jason Morris (Topher Grace). Jason is shocked when Liz turns out to be moonlighting as a phone sex operator. Liz explains that she is only doing this because she has a $100,000 student loan to pay off. Jason is upset, but eventually reconciles with her after seeing Edgar forgive Estelle.
Sean comes out on national television, and Holden, Sean’s lover, goes back to him. Kate goes home to greet her son Edison. Willy drops Felicia off at home after a date and they kiss. Kelvin and Kara hang out at Kelvin’s news station where they later kiss. Alfonso dines with his wife, and Grace and Alex agree to wait to have sex. Edgar and Estelle redo their marriage vows, Harrison eats pizza alone after Pamela leaves him, and Morley tries to call Reed, while Julia and Reed begin a romantic relationship.