Resistant hypertension is defined as blood pressure uncontrolled to guideline levels despite the use of ≥3 antihypertensive medications. When evaluating patients with resistant hypertension, it is important to consider issues such as blood pressure measurement technique, lifestyle, other comorbid conditions and medications, and the white coat effect. To this point, potential contributing factors include obstructive sleep apnea, excess alcohol intake, and use of blood pressure-elevating medications, such as nonsteroidal anti-inflammatory drugs, sympathomimetics, certain anorexic agents, and oral contraceptives. Secondary causes of hypertension are common in patients with resistant hypertension and appropriate screening tests should be performed as suggested by signs, symptoms, and laboratory abnormalities. In this regard, there is increasing evidence that hyperaldosteronism is common in the resistant hypertensive patient group. Pharmacologic therapy in patients with resistant hypertension is centered on drug combinations that have different mechanisms of action, including diuretics, which are essential in maximizing antihypertensive effects. The role of mineralocorticoid receptor antagonists is expanding, especially in patients with the metabolic syndrome, where aldosterone excess is increasingly recognized as an etiology of resistant hypertension. Finally, when appropriate, specialist referral may be necessary to appropriately assess and treat these patients.