Access to calorie-dense foods, medicine, and other comforts has made modern humans healthier than our prehistoric ancestors in many respects. However, the epidemics of obesity, diabetes, and cardiovascular disease suggest that there are also drawbacks to modern living. Here, we address the question of whether the dramatic cultural changes that have occurred over the past century have inflated rates of postpartum depression, adding postpartum depression to the list of “diseases of modern civilization.” We review evidence from cross-cultural, epidemiological, and experimental studies documenting associations between postpartum depression and modern patterns of early weaning, diets deficient in essential fatty acids, low levels of physical activity, low levels of sun exposure, and isolation from kin support networks, all of which mark significant divergences from lifestyles believed to have been typical throughout human evolutionary history. This “mismatch hypothesis” of postpartum depression integrates research across diverse research areas and generates novel predictions. [ABSTRACT FROM PUBLISHER]