The treatment of heart failure with angiotensin-converting enzyme inhibitors has resulted in substantial improvements in morbidity and mortality due to heart failure. Varying reports in the literature have suggested that African Americans respond less well to angiotensin-converting enzyme inhibitors, but careful reanalysis of major clinical trials in heart failure, especially the Studies of Left Ventricular Dysfunction (SOLVD), demonstrates a similar mortality benefit for African Americans as for whites. Morbidity, measured as hospitalizations, may not be as favorably impacted. African Americans do respond to angiotensin-converting enzyme inhibitors as a preemptive strategy to prevent heart failure, but the incidence of heart failure is still higher in this population. Mechanisms for these potential nuances in the response to angiotensin-converting enzyme inhibitors are not yet clear. The exaggerated benefit of nitrates and hydralazine implicates alterations in nitric oxide homeostasis. Race is an inadequate model to explain the observed differences. Careful translational research focusing on genetic patterns of disease may help resolve these outstanding questions.