Nick Marshall is a Chicago advertising executive who grew up with a Las Vegas showgirl as a mother. All his life, he's been showered in women's attention which made him a chauvinist who thinks of himself as God's gift to women. He is skilled at selling to men and seducing women. All men sees him as the alpha male and all women seem to approve of his ways. But just as he thinks he's headed for a promotion as the new creative director, his manager, Dan, informs him that he is hiring Darcy McGuire instead,a woman with a reputation for being a man-eater, to broaden the firm's appeal to women. A market Nick knows nothing about.
Also, his estranged 15-year-old daughter Alex is spending two weeks with him while his ex-wife Gigi goes on her honeymoon with her new husband. Alex is embarrassed by Nick's ways toward women, and resents him a lot for his lack of interest in her over the years.
On her first day at work, Darcy gives all her employees, including Nick, a box of feminine products and expect them to come up with ideas to sell those. Needing to prove himself to Darcy and Dan, Nick tries them on at home trying to come up with ideas and getting drunk in the process. As a result, he slips and falls into his bathtub while holding an electric hairdryer, shocking himself to unconsciousness.
The next day, Nick wakes up able to hear his maid's thoughts as she cleans his apartment. As he walks through a park and encounters numerous women, he realizes that he can hear their thoughts, even those of a female poodle. It gets worse when he goes to work and realizes that all his female co-workers hates him, including the ones that were really nice to him. He then runs to a previous therapist, Dr. Perkins who, he finds out, hates him as well. At first, she doesn't believe him but he's able to prove to her that he can hear her every thoughts. She then helps him realize the magnitude of his new gift: "If Men are from Mars and Women are from Venus, and you can speak Venusian, the world can be yours."
Armed with that new perspective, Nick starts eavesdropping on women's thoughts and uses their ideas as inspirations for his own campaigns. In the meantime, he also begins to develop real friendships with his female co-workers. Nick also realizes that Darcy is a very effective and capable creative director. He decides to use his new ability to get closer to Darcy in order to eventually subdue her and get her job. Which works perfectly at first, but as he spends more time with Darcy, he finds himself being attracted to her.
Meanwhile, he tries to get closer to his daughter, but she resents him for trying after so many years of neglect. He is finally able to bond with her a little by helping her shop for a dress for a prom dance. After shopping, they have a conversation in which Nick shrewdly suspects that her boyfriend, who's 18 years old, plans to sleep with her and then dump her. He tries to give her the sex talk about not doing it if you're not ready and waiting for the right guy, but she doesn't want Nick's advice.
Nick finds a new perk to his new power when he goes to seduce Lola, a coffee shop attendant who always refused his advances before. They go on a date and Nick uses his power to make it the perfect date for her. She brings him back home to have sex but Nick finds himself unable to do the deed properly because he keeps hearing her criticizing his every move. He takes a moment to regroup and goes back to the charge. We don't really know what he did differently but, in the end, she calls him, in her mind, a sex god and Nick is very proud of that.
After that, Nick and Darcy begin to spend more time together, and ultimately one night, they kiss. On his way back home, Nick finds a distraught Lola who hasn't heard from him in a week, asking for answers. Knowing there's only one answer that will not hurt Lola or make her feel rejected, Nick plays along with Lola's thoughts and admits to her that he is very gay.
Nick starts to feel bad about himself and what he's doing to Darcy. He not only sees the error of his ways but the error of men's ways toward women in general. Especially when he manages to trump Darcy out of her ideas for a new Nike ad campaign aimed at women, which leads to a very lucrative contract for the firm but also to Darcy being fired and Nick being promoted.
Nick finally step-up to the plate and confronts his boss about firing Darcy. He convinces him that all his ideas were hers and he should take her back which he agrees to.
Nick is about to go to Darcy's to explain everything when he finds out that Erin, one of the office secretaty who's suicidal thoughts Nick heard on many occasions, has not showed up for work and hasn't called either. Convinced of the worst Nick goes to Erin's hoping to stop her. On his way, Nick witness an electrical explosion while standing in the rain. He goes to Erin and talks to her, meanwhile realizing he's not hearing her thoughts anymore and concluding he lost his gift. He then goes to Darcy's but is unable to reach her and leaves.
That night, He is reconciled with his daughter when her boyfriend rejected her for following Nick's advice after all. He puts his daughter to bed and goes to Darcy's in the middle of the night to finally confess everything. She first fires him, which Nick never saw coming but realizes he deserves it and accepts it. She then forgives him and agrees to save him from himself, to which he responds "My hero" and they kiss.