Sex differences in parasite infection rates, intensities, or population patterns are common in a wide range of taxa. These differences are usually attributed to 1 of 2 causes: (1) ecological (sociological in humans); and (2) physiological, usually hormonal in origin. Examples of the first cause include differential exposure to pathogens because of sex-specific behavior or morphology. The second cause may stem from the well-documented association between testosterone and the immune system; sexually mature male vertebrates are often more susceptible to infection and carry higher parasite burdens in the field. Although many researchers favor one explanation over the other, the requisite controlled experiments to rule out confounding variables are often neglected. We suggest that sex differences in disease have evolved just as sex differences in morphology and behavior, and are the result of selection acting differently on males and females. Research has often focused on proximate mechanistic explanations for the sex difference in infection rates, but it is equally important to understand the generality of the patterns in an evolutionary context. Because males potentially gain more than females by taking risks and engaging in competition, sexual selection pressure has shaped male behavior and appearance to maximize competitive ability and attractiveness. Many of the classic male attributes such as antlers on deer are testosterone-dependent, putting males in what appears to be a cruel bind: become vulnerable to disease by developing an attractive secondary sexual ornament, or risk lowered mating success by reducing it. A variety of hypotheses have been put forward to explain why males have not circumvented this dilemma. The mating system of the host species will influence the likelihood of sex differences in parasite infection, because males in monogamous species are subject to weaker sexual selection than males in polygynous species. Whether these evolutionary generalizations apply to invertebrates, which lack testosterone, remains to be seen.