Patients with resistant hypertension are those who have uncontrolled blood pressure despite use of three or more antihypertensive medications, or those who require four or more medications to achieve control. When evaluating resistant hypertension it is important to rule out pseudoresistant hypertension that may result from factors including poor blood pressure measurement technique and the white coat effect. Potential contributing factors should be identified and reversed if possible, including obesity, excess alcohol intake and use of interfering medications such as NSAIDS, sympathomimetics and oral contraceptives. Modification of lifestyle factors such as weight loss, sodium restriction and physical activity is paramount for treatment success. Secondary causes of hypertension are common in this patient group and, therefore, appropriate screening tests should be carried out as necessary. Pharmacologic therapy is centered on combination therapy of medications from different mechanisms of action, especially diuretics, which are essential in maximizing antihypertensive effects. The role of mineralocorticoid antagonists is expanding, especially in patients with obstructive sleep apnea and obesity where aldosterone excess may be implicated. Finally, when appropriate, specialist referral may facilitate blood pressure reduction and the ability to meet target blood pressure goals. © 2009 Expert Reviews Ltd.