Coronary artery disease (CAD) is the leading cause of death in African Americans, despite the lower prevalence of anatomic coronary atherosclerosis in this group. Risk factors for CAD in African Americans are considerable; however, the specific role of these risk factors in the excess mortality rates as compared with that of whites is not clarified. Factors such as differences in vascular pathobiology may be important in determining the cause of the excess mortality. The higher prevalence of normal coronary angiograms in African Americans with angina may be caused by pathobiology related to microvascular function and reserve. When access is available, the initial approach to diagnoses and management of coronary artery disease in African Americans is no different from that in other populations. Diagnostic approaches and therapeutic interventions are needed to identify the cause and modify the effects of the excess risks from coronary artery disease in African Americans.