Renal artery stenosis (RAS) is usually observed in hypertensive patients with extensive atherosclerosis. There is some evidence that in these patients the atherosclerotic process and the consequent target-organ damage is more severe than in hypertensive patients without RAS. In this review we will entertain the hypothesis that some of the humoral factors that are activated by RAS may contribute to accelerate the progression of atherosclerosis. Several studies identified RAS as a predictor of cardiovascular events in high-risk patients, although in most cases the contribution of blood pressure per se to the progression of vascular lesions could not be determined. As a result of experimental RAS, hypertension and increased oxidative stress are stimuli for atherosclerosis as well as cardiac and renal damage. In the presence of RAS, the renin-angiotensin system is stimulated, and it has been shown that angiotensin II exerts proinflammatory, pro-oxidant and procoagulant activities in experimental models and humans. The potential contribution of reactive oxygen species to the prohypertensive and proatherosclerotic effects of RAS is supported by evidence that nicotinamide adenine dinucleotide phosphate, reduced form oxidase is specifically stimulated by angiotensin II, an activity not shared by epinephrine. Moreover, angiotensin II triggers the release of aldosterone, endothelin 1, thromboxane A2 and other derivatives of the arachidonic acid metabolism, all of which can further and independently aggravate cardiovascular damage. Epidemiological and experimental evidence so far available suggests that accelerated atherosclerosis can be both the cause and the consequence of RAS.