Hypertension affects 60 million Americans and is the most common disorder for which medications are prescribed in the USA. Hypertension associates with serious complications including stroke, heart failure, ischemic heart disease, and renal failure. Racial background associates with the prevalence and complications of hypertension with African Americans more frequently and severely affected. Hypertensive African Americans demonstrate different responses to antihypertensive medications compared to other ethnic groups and specific candidate gene polymorphisms associate with the responses found. Differences between African Americans and other racial groups are present with regard to endothelial dysfunction and activation of the renin-angiotensin-aldosterone system. In addition the frequency of polymorphisms of genes involved in the regulation of endothelial function and the renin-angiotensin-aldosterone system differ between African Americans and other ethnic groups. This review highlights the current information available with regard to the genetics of hypertension in African Americans with particular attention to pharmocogenomic studies of antihypertensive therapy.