Reed Bennett (ASHTON KUTCHER) is a third generation florist in Los Angeles, so he's used to seeing the crazy business that Valentine's Day brings to his shop. Yet, he wants a life like his best buddy and employee, Alphonso (GEORGE LOPEZ), who's happily married. Accordingly, Reed proposes to his live-in girlfriend, Morley Clarkson (JESSICA ALBA), thus making his best friend, Julia Fitzpatrick (JENNIFER GARNER), happy for him. She's an elementary school teacher who thinks she's found Mr. Right in heart surgeon Dr. Harrison Copeland (PATRICK DEMPSEY) who says he's off to San Francisco for surgery.
That leaves her alone for Valentine's Day, thus meaning she'll likely attend an anti-Valentine's Day party thrown by her friend Kara Monahan (JESSICA BIEL). She's the publicist for professional quarterback Sean Jackson (ERIC DANE) who, at the age of 35, finds his career winding down, much to the chagrin of his agent, Paula Thomas (QUEEN LATIFAH). TV sports reporter Kelvin Moore (JAMIE FOXX) would love the scoop on Sean, but his producer, Susan (KATHY BATES), has assigned him to do a love-related segment, which is ironic since his mindset about this February day is perfectly aligned with Kara.
Yet, there are those in love, including Liz (ANNE HATHAWAY), Paula's new secretary who secretly moonlights as a phone sex operator, completely unknown to her boyfriend of several weeks, Jason (TOPHER GRACE), who works in the mailroom in her office. While they've consummated their relationship, high school students Grace (EMMA ROBERTS) and Alex (CARTER JENKINS) are planning on doing the same for the first time, unlike their best friends, Willy (TAYLOR LAUTNER) and Felicia (TAYLOR SWIFT), who are also a mad-in-love couple but are holding off.
Grace is the babysitter for Edison (BRYCE ROBINSON), a 5th grader in Julia's class and who's paid Reed to deliver flowers to his secret valentine. He lives with his grandparents, Edgar (HECTOR ELIZONDO) and Estelle (SHIRLEY MACLAINE), who've been married for 51 years but are about to hit a bump in their long-term relationship.
Meanwhile, headed toward L.A. on a long flight is Holden (BRADLEY COOPER), a handsome man who strikes up a conversation with the woman in the seat next to him, U.S. Army Capt. Kate Hazeltine (JULIA ROBERTS) who's headed home for a quick visit to see the most important guy in her life. As the day plays out, they and everyone else must deal with the pleasures and pressures that Valentine's Day brings for them and those they love.