Andy Stitzer (Steve Carell) is the 40 year old virgin of the title. While a very pleasant and well-meaning guy, he is something of a stereotypical nerd, as he lives alone, collects action figures, enjoys video games, rides a bike, and his social life seems to consist of watching Survivor with his elderly neighbors. And, of course, he has never had sex.
Andy works in the stockroom at an electronics store called SmartTech. His co-workers include the affable David (Paul Rudd), who is tormented by memories of his old girlfriend Amy (Mindy Kaling); the burly Cal (Seth Rogen), a self-proclaimed novelist and stoner; and Jay (Romany Malco), who is something of a ladies man and straight gangsta. One night, these three ask Andy to play poker with them (purely for lack of anyone else to invite). While swapping sex stories during the game, they quickly figure out that Andy is still a virgin, and resolve to help him lose his virginity.