Improved technology for detection of and endovascular procedures for renal artery stenosis due to atherosclerosis has been associated with increases in renal artery intervention. Hypertension with accelerated target organ injury, reduced kidney function, and episodic circulatory congestion in patients with renovascular disease predict reduced patient survival. Recent studies indicate that activation of pressor mechanisms depends upon hemodynamic gradients that are often overrated by visual estimates. Although activation of the renin-angiotensin system initiates renovascular hypertension, additional mechanisms perpetuate vascular remodeling and kidney injury that may not depend upon large vessel occlusion. Major advances in medical therapy have led to initiation of at least 4 major prospective trials comparing optimal medical therapy with or without stenting. Up to now, outcome data fail to support broad application of renal revascularization, including results from a recent large, prospective trial from the United Kingdom, despite small groups of patients that experience major clinical benefit. The ambiguity of these results partly reflect poor characterization of the severity of vascular lesions and competing risks within the population related to aging and pre-existing disease. Many patients currently undergoing renal artery interventions derive little net benefit and some are exposed to significant complications, including atheroembolic disease. Determining the appropriate role for renal artery interventions will depend on developing better methods for judging the role of large vessel occlusive disease regarding tissue oxygenation, activation of profibrotic pathways, and irreversible injury in the post-stenotic kidney.