This article provides an overview of the evidence on the ways racism can affect the disproportionate rates of cardiovascular disease (CVD) in African Americans. It describes the significant health disparities in CVD for blacks and whites and suggests that racial disparities should be understood within the context of persistent inequities in societal institutions and relations. Evidence and potential pathways for exploring effects of 3 levels of racism on cardiovascular health risk factors and outcomes are reviewed. First, institutional racism can lead to limited opportunities for socioeconomic mobility, differential access to goods and resources, and poor living conditions that can adversely affect cardiovascular health. Second, perceived/personally mediated racism acts as a stressor and can induce psychophysiological reactions that negatively affect cardiovascular health. Third, in race-conscious societies, such as the United States, the negative self-evaluations of accepting negative cultural stereotypes as true (internalized racism) can have deleterious effects on cardiovascular health. Few population-based studies have examined the relationship between racism and CVD. The findings, though suggestive of a positive association, are neither consistent nor clear. The research agenda of the Jackson Heart Study in addressing the role of racism in CVD is presented.