Americans lead shorter and less healthy lives than do people in other high-income countries. We review the evidence and explanations for these variations in longevity and health. Our overview suggests that the US health disadvantage applies to multiple mortality and morbidity outcomes. The American health disadvantage begins at birth and extends across the life course, and it is particularly marked for American women and for regions in the US South and Midwest. Proposed explanations include differences in health care, individual behaviors, socioeconomic inequalities, and the built physical environment. Although these factors may contribute to poorer health in America, a focus on proximal causes fails to adequately account for the ubiquity of the US health disadvantage across the life course. We discuss the role of specific public policies and conclude that while multiple causes are implicated, crucial differences in social policy might underlie an important part of the US health disadvantage.