Eliminating health disparities is a fundamental, though not always explicit, goal of public health research and practice. There is a burgeoning literature in this area, but a number of unresolved issues remain. These include the definition of what constitutes a disparity, the relationship of different bases of disadvantage, the ability to attribute cause from association, and the establishment of the mechanisms by which social disadvantage affects biological processes that get into the body, resulting in disease. We examine current definitions and empirical research on health disparities, particularly disparities associated with race/ethnicity and socioeconomic status, and discuss data structures and analytic strategies that allow causal inference about the health impacts of these and associated factors. We show that although health is consistently worse for individuals with few resources and for blacks as compared with whites, the extent of health disparities varies by outcome, time, and geographic location within the United States. Empirical work also demonstrates the importance of a joint consideration of race/ethnicity and social class. Finally, we discuss potential pathways, including exposure to chronic stress and resulting psychosocial and physiological responses to stress, that serve as mechanisms by which social disadvantage results in health disparities.