Andy Stitzer is a shy 40-year-old introvert who works as a stock supervisor at the electronics store Smart Tech. He gave up trying to have sex after various failed attempts and lives alone in an apartment with a collection of action figures and video games. When a conversation at a poker game with his co-workers David, Jay, and Cal turns to past sexual exploits, they learn that he secretly is still a virgin.
Andy is mortified upon discovering the next day that everyone else at work has learned about the secret, including their boss Paula, who is attracted to him and later privately offers to take his virginity. He almost quits work in humiliation before David consoles him and recommends trying again to have sex. David, Jay, and Cal become determined to help Andy achieve this. They all give differing advice on how to interact with women.