Ecological threats impose substantial selective pressure throughout the animal kingdom, and drive the evolution of specific behavioral and social systems best suited for a given ecological niche. However, the specific role that ecological variables have played in the evolution of human behavior, cognition, and culture has only recently become a topic of rigorous empirical investigation. This paper considers the implications of one specific ecological variable—the threat of infectious disease—for individual behavior, cognition and, ultimately, the evolution of contemporary cultural differences. An emerging body of research conducted at multiple levels of analysis suggests that cross-cultural variation in the threat of disease may be responsible, at least in part, for cultural variation in personality, attitudes, and value systems. This psychological variation may also have downstream consequences for variation in institutions as well. Mechanisms that may account for these relationships and implications are discussed.