Isotope ratio mass spectrometry (IRMS) is a powerful tool for reconstructing life history trajectories, kinship patterns, migration, diet and health in ancient populations of anatomically modern humans and their predecessors. The elements that comprise bodily tissues are non-random, incorporated from food and drink and determined by isotope fractionation and tissue growth rates. To illustrate the diversity of ecological conditions and diets to which humans have adapted, this chapter focuses on isotopic data from prehistoric human diets cross-culturally and through evolutionary time, as well as accompanying skeletal indicators of morbidity and mortality. These data demonstrate the broad patterns of health and disease related to human diets and physical activity levels in our evolutionary past and provide insight into conditions that are prevalent today (e.g. obesity and diabetes) that arise from a mismatch between the mosaic ecological conditions to which humans adapted and our modern, industrialised environment. Our current biomedical models for understanding these conditions have not reduced poor health outcomes in our communities. We propose employing isotopic data from the remains of our ancestors and using a biocultural framework in medicine to move towards integrating evolutionary thought in public health policy. An anthropological framework that incorporates an understanding of dietary adaptations and evolved behavioural strategies is crucial for successful and culturally sensitive health interventions.