Resistant hypertension (RH) is defined as blood pressure above a goal despite adherence to at least 3 optimally dosed antihypertensive medications of different classes, one of which is a diuretic. Evaluation of possible RH begins with an assessment of adherence to medications. The white-coat effect should be ruled out by out-of-office blood pressure monitoring. Obesity, heavy alcohol intake, and interfering substances all contribute to RH. Dietary sodium restriction is an important part of management. RH may be secondary to problems such as renal disease, obstructive sleep apnea, or aldosteronism, and testing for these conditions should be considered. Adequate diuretic treatment is a key part of therapy. Chlorthalidone is more effective than hydrochlorothiazide in reducing blood pressure because it is more potent and lasts longer. In addition, it may reduce cardiovascular events to a greater extent than hydrochlorothiazide. When glomerular filtration rate is <30 mL/min, a loop diuretic usually is needed. The addition of spironolactone, with careful attention to potassium levels, is an evidence-based strategy for the treatment of RH. Other strategies include use of a vasodilating β-blocker, adding a long-acting nondihydropyridine calcium channel blocker, or adding clonidine. When blood pressure is not coming under control despite 4 or 5 agents, referral to a hypertension specialist may be warranted.