Charlie kot deček ni hotel poljubiti zmešane punce, zato ga je ona užaljena uročila, da ne bo nikoli našel prave ljubezni. Dvajset let kasneje je Charlie uspešni zobozdravnik, ki pa kljub številnim ljubicam nikakor ne najde ženske, s katero bi si ustvaril družino. Pravzaprav odkrije, da je še vsaka ženska, s katero je spal, v svojem naslednjem moškem našla bodočega moža. Nič čudnega torej, da Charlie postane tarča vseh žensk, ki si obupano želijo spoznati pravega in bi zato rade najprej spale z njim. Vse se spremeni, ko Charlie spozna znanstvenico Cam, za katero je prepričan, da je ženska njegovega življenja.
Early thirty-something dentist Dr. Charlie Logan has never experienced true love, despite having had a number of girlfriends over the years. After an announcement by one of his ex-girlfriends as such at her wedding, Charlie gets a reputation as being a good luck charm. Every woman he has slept with has met and married her dream man immediately following. He is encouraged to exploit this reputation by his long time best friend, Dr. Stu Klaminsky, a sex obsessed, sex starved schlub who became a plastic surgeon just so that he could masturbate over the sight of women's breasts. Charlie doesn't want to be solely a stepping stone for women, which is how they end up treating him once he gains this reputation as a lucky charm, but rather one's true love. He believes the woman of his dreams is accident-prone Cam Wexler, who works as the penguin caretaker at the aquarium. Cam initially doesn't want to date Charlie because of his reputation as a one-night stand type of guy. Charlie in turn doesn't want to sleep with Cam as he is certain she will find her true love after they do. Cam's true love seems destined to be penguin expert Howard Blaine. To get to true happiness, Charlie feels he needs to speak to Anisha Carpenter, who he feels is the cause of his current problems. Anisha ends up helping him in a way he doesn't expect.