Large racial/ethnic and socioeconomic status (SES) differences in health persist in the United States. Eliminating these health disparities is a public health challenge of our time. This article addresses what is needed for social and behavioral interventions to be successful. We draw on important insights for reducing social inequalities in health that David Mechanic articulated more than a decade ago in his article “Disadvantage, Inequality, and Social Policy.” We begin by outlining the challenge that interventions that have the potential to improve health at the population level can widen social inequalities in health. Next, given that there are racial differences in SES at every level of SES, we review research on race/ethnicity-related aspects of social experience that can contribute to racial inequalities in SES and health. We then explore what is needed for social and behavioral interventions to be successful in addressing disparities and consider the significance of race/ethnicity in designing and developing good policies to address this added dimension of inequality. We conclude that there is a pressing need to develop a scientific research agenda to identify how to build and sustain the political will needed to create policy to eliminate racial/ethnic health disparities.