Hypertension in African Americans is a major clinical and public health problem because of the high prevalence and premature onset of elevated blood pressure (BP) as well as the high burden of co-morbid factors that lead to pharmacological treatment resistance (obesity, diabetes mellitus, depressed glomerular filtration rate, and albuminuria). BP control rates are lower in African Americans, especially men, than in other major race/ethnicity-sex groups; overall control rates are 29.9% for non-Hispanic Black men. Optimal antihypertensive treatment requires a comprehensive approach that encompasses multifactorial lifestyle modifications (weight loss, salt and alcohol restriction, and increased physical activity) plus drug therapy. The most important initial step in the evaluation of patients with elevated BP is to appropriately risk stratify them to allow determination of whether they are truly hypertensive and also to determine their goal BP levels. The overwhelming majority of African American hypertensive patients will require combination antihypertensive drug therapy to maintain BP consistently below target levels. The emphasis is now appropriately on utilizing the most effective drug combinations for the control of BP and protection of target-organs in this high-risk population. When BP is >15/10 mmHg above goal levels, combination drug therapy is recommended. The preferred combination is a calcium antagonist/angiotensin-converting enzyme inhibitor or, alternatively, in edematous and/or volume overload states, a thiazide diuretic/angiotensin-converting inhibitor.