The journey of atherosclerosis begins with endothelial dysfunction and culminates into its most fearful destination producing ischemia, myocardial infarction and death. The excess cardiovascular disease morbidity and mortality in African-Americans is one of the major public health problems. In this review, we discuss vascular endothelial dysfunction as a key element for excess cardiovascular disease burden in this target population. It can be logical window of future atherosclerotic outcomes, and further efforts should be made to detect it at the earliest in African American individuals even if they are appearing healthy as the therapeutic interventions if instituted early, might prevent the subsequent cardiac events.