Abby Barnes is a veterinarian, who hosts a Los Angeles radio show called "The Truth About Cats and Dogs." The use of this as the title of the film also suggests the combative nature of male-female romantic relationships. Abby strikes up an unexpected friendship with her neighbour Noelle Sluslarsky, a traditionally-attractive model who is sweet, but not very sharp. When Abby makes a blind date with a caller to her show, her insecurity with her own appearance leads her to convince Noelle to pretend to be Abby when meeting the date. Unfortunately, both women develop feelings for the man, leading to a comedic series of misunderstandings, as their unintentional deception grows deeper.