This chapter reviews recent data on the evolution of sexual strategies in humans and shows how, in the natural environment, the adaptive functions of sexual infidelity were substantially different in males and females. The meaning of technical terms used by evolutionary biologists to describe different behavioral strategies related to maximization of reproductive success are explained, including the Coolidge effect, good-gene sexual strategy, and serial monogamy. Biological analysis of motivations for sexual infidelity integrate evolutionary hypotheses with recent data from molecular genetic studies of personality showing that carriers of some genetic polymorphisms related to novelty seeking are more prone to sexual promiscuity. Finally, the chapter reports a clinical case showing how cultural prejudice can distort individual expectations about what is normal sexual desire.