Cardiovascular disease (CVD) is the No. 1 cause of mortality in the United States and it disproportionately affects African Americans. However, there are earlier reports that African Americans had significantly less CVD than whites. This racial discrepancy in CVD rates was noticed primarily for coronary heart disease (CHD). This issue was examined in the Evans County (Georgia) Cardiovascular Disease Study conducted in the 1960s. It showed that African American men had significantly lower rates of CHD than white men. Over the last couple of decades, the rates of CVD have been declining. However, the rate of decline of CVD in African Americans has not been equal to that seen in whites, such that African Americans now have a disproportionate share of CVD in the United States. In the 1990s, the Jackson Heart Study was designed to explore the reasons for the current racial discrepancy. This articles reviews the findings of the Evans County Study and explores various hypotheses for why CVD in African Americans has evolved from a disease from which African Americans may have been “protected” to one in which they shoulder a disproportionate burden.