Jamie Randall (JAKE GYLLENHAAL) is a natural born salesman and ladies man, but his amorous ways have lead to him being fired from his latest job. Unlike his younger brother, Josh (JOSH GAD) who made a fortune from a stock IPO, Jamie has no money to fall back on, and thus gets a sales rep job for a major pharmaceutical company.
Paired with veteran sales rep Bruce Winston (OLIVER PLATT), Jamie hits the road, trying to sell his company's wares to the likes of general practitioner Dr. Stan Knight (HANK AZARIA). To get to him, he sweeps one the doc's receptionists, Cindy (JUDY GREER), off her feet, but she becomes jealous when Jamie obviously shows interest in one of Stan's patients.
She's 26-year-old Maggie Murdock (ANNE HATHAWAY), a pretty woman who's facing her early onset Parkinson's Disease with humor and a willingness to live life to the fullest, including sleeping around. One of her last lovers was Trey Hannigan (GABRIEL MACHT), a sales rep for a rival pharmaceutical company that's also after the likes of Stan, but that doesn't stop her from bedding Jamie with the caveat that everything remains casual.
Yet, as he finally wins a way in to become Stan's favorite sales rep -- via a new little pill known as Viagra -- Jamie finds himself falling for Maggie, much to her dismay, although she eventually starts to feel the same way. With them facing an uncertain future -- regarding his career potential and her disease -- they have to figure out what's going to happen with them.