The life history of human hunter-gatherers is characterized by an extended post-reproductive lifespan, prolonged juvenile growth, high fertility with multiple dependents and biparental care, and extensive intra- and inter-generational resource and information transfer. Long-term, indepth study of contemporary non-industrial populations offers important glimpses into how these traits operate, and insights into how they may have evolved. The Tsimane Health and Life History Project is a large-scale bio-behavioral study of the human life course designed to help understand the bidirectional connections between life history, health and social behavior in a high fertility, kin-based population lacking amenities of modern urban life. It seeks to document the epidemiology of health and mortality across the lifespan, and to understand how growth and investment, social structure, sharing networks and behavior impact health and aging. It focuses on how pathogen burden influences health and well-being during development and adulthood, and addresses how modernization affects health and sociality. We reflect on the implications of current findings and highlight the need for more joint ethnographic and biomedical studies of subsistence populations to address unresolved questions not only in evolutionary anthropology or biodemography, but in public health, epidemiology, gerontology and medicine.