The clinical diagnosis of renal artery stenosis relies on a high index of suspicion and confirmation by noninvasive imaging modalities. There are three distinct clinical syndromes associated with renal artery stenosis: renin-dependent hypertension, essential hypertension, and ischemic nephropathy. Clinical features that should heighten suspicion for renal artery stenosis include abrupt-onset or accelerated hypertension at any age, unexplained acute or chronic azotemia, azotemia induced by angiotensin-converting enzyme (ACE) inhibitors, asymmetric renal dimensions, and congestive heart failure with normal ventricular function. Patients with true renin-dependent (renovascular) hypertension are typically young or middle-age women with renal fibromuscular dysplasia (FMD). Initial therapy for renovascular hypertension associated with FMD is an ACE inhibitor; refractory hypertension responds readily to balloon angioplasty without stenting. Elderly patients with generalized atherosclerosis and hypertension often have atherosclerotic renal artery stenosis (ARAS); hypertension in these patients is usually not renin dependent (ie, essential hypertension). Hypertension alone, even if treated with multiple medications, is not a compelling indication for renal artery revascularization; these patients should be treated aggressively with antihypertensive medical therapy. Renal artery revascularization with stenting may be considered for refractory severe hypertension, and would be expected to improve blood control and modestly reduce medication requirements. Renal revascularization rarely cures hypertension in patients with ARAS. Patients with ARAS, hypertension, and end-organ injury should be considered for renal revascularization. Manifestations of end-organ injury include nonischemic pulmonary edema; hypertensive crisis associated with acute coronary syndrome, aortic dissection, or neurologic impairment; and renal insufficiency. Ischemic nephropathy is best treated before the development of advanced renal failure. The best candidates for revascularization are those with baseline serum creatinine less than 2.0 mg/dL, bilateral renal artery stenosis, normal renal resistive indices, no proteinuria, and one or more manifestations of end-organ injury. In these patients, renal revascularization is best accomplished by stenting, although surgical revascularization may be considered in patients with concomitant severe aortic aneurysmal or occlusive disease.