The movie starts with a voice over of Jane Goodal (Ashley Judd) over the images of a scientific experiment with a bull and a herd of cows, apparently the bull never mounts a cow twice, not even if her scent is changed. He prefers a new cow.
Jane tells us that until recently she believed that men are all like the bull, but to understand what happened we have to go back in time.
Jane is a production assistant with a talk show that has recently been syndicated, which means that the host Dianne Roberts (played by Ellen Barkin) who wants to be the best, is always looking for the ungettable guests, like Fidel Castro.
Eddie Alden (Hugh Jackman ) is the producer of the talk show and is a womaniser, much to the dismay of Jane and she comments on his actions with amicable critique.
Eddie is looking for a roommate but his messages on the bulletin board are sabotaged by disgruntled exes, he wonders whether she wouldnt like to move in, she turns him down with a vengeance.
Then they meet the new producer of the show Ray Brown (Greg Kinnear) and Jane is immediately smitten.
She tells her friend Liz (Marisa Tomei) and discuss her bad luck with men.
Meanwhile her sister and is trying to get pregnant with a fertility program.
Ray calls Jane and they spend a evening together and end up kissing, the next morning she calls Liz and is ecstatic Liz gives her some advice as to how to deal with Ray and his girlfriend Dee (with whom he has trouble).
Ray and Jane are very much in love and the relationship evolves and they decide to move in together Jane puts in her notice, he goes to tell his girlfriend it is over, but doesnt tell her about the new woman in his life.
Ray starts to get distant while Jane is packing to move over, and over dinner he breaks it of, leaving Jane in tears.
The next morning in the office Jane takes her revenge by announcing to move in with Eddy.
She learns to deal with the many women in Eddys life, they bond over scotch and old Chinese food.
She reads an article about the old cow syndrome and starts researching for her theory of men .
Liz works at a magazine for men and needs a columnist and persuades Jane to write a column about her theory, under a pen name Dr Marie Charles.
The column that deals with the insecurity and dishonesty of men is a big hit, everybody wants to meet Dr Charles, so does Dianne.
At a Christmas party Ray tells her he misses her and asks her out for new years eve, but he doesn't show. When Jane shows up at a party looking for Eddy at midnight she cant find him and she leaves in tears Eddy tries to go after her but cant find her, and disappointed sits on the outside steps.
Back at the office Ray tries to apologise but Dianne interrupts wearing a shirt Jane bought for Ray, she is Dee, and Ray is back with her.
A boardmeeting is going to start and Eddy makes sure Jane isnt crying going in, but Jane is distracted and he covers for her, when Ray shows emotion over a Gerard Depardieu movie, Jane spill her guts over his inability to show empathy for her broken heart.
Dianne, unaware of Janes relationship with Ray, gives her advice on how to win her boyfriend back, telling her how she got hers back.
At a bar Liz follows Dr Charles advice and is not going to fall for the same kind of guy anymore. Jane and Eddy get into a fight over the advice of Dr. Charles, back home she tells him she has to believe the theory because otherwise she is afraid that men don't leave women they leave her.
Eddy comforts her by saying Ray is not the last man she'll ever love, and they fall asleep together, the next morning Eddy wakes up happy and comfortable, Jane freaks out.
Eddy tells her not to analyse this too, he is happy he slept the whole night with her without it leading to sex.
She tells Eddy he will show his true colours and will hurt her some time soon, Eddy tells her it is not about him but it is her attitude that is the problem.
Jane gets a call and it is her brother in law telling her that they lost the baby.
At the hospital she sees the true love between her and decides to tell Dianne that Dr Charles is going to be on her show.
The interview is meant to be over the telephone but Jane changes her mind and goes on the stage, she tells the audience that there is no Dr (we see Eddy leave at this stage) and that the theory is ridiculous because she was hurt and needed to blame the men for her pain.
But not all men are animals, some will be there for you and tell you that Ray isnt the last one youll ever love. By this time Eddy is long gone.
Jane goes after Eddy and finds him when he is taking a taxi, she gets him out of the taxe and tells him she found new love, and he doesnt answer but kisses her with passion.