African Americans have higher rates of cardiovascular disease (CVD) than Whites and the racial gap in heart disease is widening over time. There are especially striking patterns of the earlier onset of disease, greater severity of illness and large racial differences in CVD even when Blacks and Whites are compared at the same level of economic status. This paper outlines critical research opportunities for the Jackson Heart Study to advance the science base for understanding and effectively addressing racial disparities in CVD. These include: 1) the study of CVD by using a life course perspective; 2) comprehensively characterizing social stressors; 3) expanding our analysis of how racism affects health; 4) explicating variation in the levels and impact of risk factors; 5) advancing our understanding of the contribution of genetics to CVD; 6) understanding resilience and its effects on CVD; and 7) identifying how economic crises can shape CVD risk.