Evolutionary principles inform central design features of human immune defenses and provide key insights into this complicated host defense system. This article explores the selection pressures and adaptive responses that have elaborated the immune system over the course of evolution and discusses their implications for understanding contemporary immune development and function. Special attention is given to the challenges posed by diverse, rapidly evolving pathogens and the mammalian response to these challenges. The process of lymphocyte diversity generation and subsequent clonal selection is quintessentially Darwinian: pathogens provide selection pressure that drives differential replication of host immune cell lines, resulting in changes in genetic frequencies within an individual's population of lymphocytes. The immune system also incorporates nongenetic transgenerational processes in the transfer of antibodies from mother to offspring through the placenta and breast milk. The consequences of these observations for human development, health, and the ecology of immune function are considered throughout the life cycle. Specifically, evolutionary processes provide insight into autoimmunity, thymic function, lymphocyte development, infectious disease risk, and lactation. While much work in evolutionary medicine focuses on the discordance between evolved biology and rapidly changing cultural environments, with respect to the immune system, evolutionary processes may be most revealing when applied within individuals. Am.