Mary Horowitz (SANDRA BULLOCK) creates weekly crossword puzzles for the Sacramento Herald but doesn't have any sort of personal life. The fact that she lives at home with her parents (BETH GRANT and HOWARD HESSMAN) while her place is fumigated certainly doesn't help matters, and she isn't looking forward to the blind date they've arranged for her.
That changes, however, when she sets eyes on Steve Gunders (BRADLEY COOPER), a cameraman for the CCN TV network who works with producer Angus (KEN JEONG) getting reporter Hartman Hughes (THOMAS HADEN CHURCH) on the air. Immediately smitten, she tries seducing him in the first minutes of their date, and while he's sort of into that, her non-stop talking and trivia dropping quickly changes his mind. Fortunately for him, an urgent work call means he has to leave, but not before saying something she takes out of context as meaning he's interested in her when he really isn't.
The next day, her crossword puzzle is all about him, resulting in her boss firing her. Yet, in her mind, that frees her up to join Steve on the road, and thus she sets off to find him as his team covers the latest breaking new stories for their boss, Danny (KEITH DAVID). After she barely misses them when a hostage situation is resolved, she follows them to another location where they're covering the news story of a girl born with three legs.
There, she meets a number of protestors, including Elizabeth (KATY MIXON) and Howard (DJ QUALLS), who want the girl to keep her limbs. When not the on air competing with rival reporter Vasquez (JASON JONES) for that and other stories, Hartman decides to mess with Mary by leading her on that Steve truly is into her, and that anything he says to the contrary is just him being insecure.
From that point on, and as they end up traveling around the country, Mary continues with her belief that she's meant to be with Steve, all as his horror of being stalked continues to grow.