Chronic heart failure (CHF) is a common disease with high associated morbidity and mortality, and the outcome appears to be worse in black compared with white patients. There is currently no clear consensus for basing the pharmacological treatment of CHF on racial differences. Most studies that have investigated the potential effects of racial differences on pharmacological responses in heart failure have been based on African Americans and white participants. Using these data, this review will discuss the current understanding of the effects of racial differences in response to pharmacotherapy in heart failure, possible mechanisms for these observed differences, and how this may impact on patient management. Diuretics have favorable symptomatic benefits in both black and white patients with heart failure with evidence of fluid retention. ACE inhibitors seem to be less effective in the treatment of black patients with heart failure compared with white patients. This may be due to low pre-existing activity of the renin-angiotensin system in blacks. The role of angiotensin receptor blockers (ARBs) in the management of all patients with heart failure is incompletely defined and there are no clear trial data to show any difference in effect between black and white patients with heart failure. There is good evidence for the use of spironolactone in all patients with heart failure, but no evidence for a different effect in black patients. Similarly, there is no conclusive data to suggest a difference in effect of digoxin in different racial groups. The evidence available would suggest that certain beta-adrenoceptor antagonists (certainly carvedilol but not bucindolol) are effective in both black and white patients with CHF. The combination of hydralazine and nitrates would appear to be particularly effective in black patients with CHF though the African American Heart Failure Trial (A-HeFT) trial should provide clearer evidence for the potentially greater beneficial effects of these two drugs in the black population. It is important to accept that racial categorization acts as only a surrogate marker for genetic or other factors responsible for individual responses to drug therapy and that any identified differences will not apply to all members of each stratified group. Nonetheless, in managing a complex, common and often fatal condition such as heart failure, recognizing potential individual differences in drug responses should enable the responsible clinician to provide a tailored and evidence-based approach to patient treatment.