Background: Renal artery stenosis (RAS) has a high prevalence in older patients, especially in the context of general atherosclerosis. It is frequently associated with resistant hypertension and impaired renal function and their attendant consequences. The issue whether revascularization via percutaneous renal angioplasty and stenting (PRA/S) can benefit these patients remains unsettled., Objective: To present a case series of patients with refractory hypertension and RAS undergoing PRA/S and also to provide an extensive review of the literature on the current status of PRA/S for resistant hypertension., Methods: Data of all consecutive patients undergoing PRA/S by a single operator over 1 year were prospectively collected. These were 9 patients with hypertension refractory to drug therapy who also had other clinical cardiac problems that led to their hospitalization, including flash pulmonary edema and coronary artery disease. They were all receiving ≥3 antihypertensive drugs and renal angiography revealed critical RAS (unilateral in 3 and bilateral in 6). In addition, an extensive literature review of the topic was carried out in PubMed, Scopus and Google Scholar., Results: PRS was successful in all 9 high-risk RAS patients with resistant hypertension (5 men, mean age 71 years) without complications and helped in bringing under control their elevated blood pressure (BP) and in maintaining their renal function over a mean of 21 months. Literature review of this controversial topic indicates that in carefully selected patients, PRA/S may play an important role in controlling BP, alleviating symptoms and perhaps preventing renal failure, albeit without concrete evidence of significantly affecting hard end-points of renal events, major cardiovascular events and death. Randomized controlled studies (RCTs), including a large one (CORAL trial), although heavily criticized, have not provided evidence in favor of revascularization. Although RCTs are rather neutral, a multitude of prospective, observational cohort studies, comparing the outcomes of patients after PRA/S have demonstrated significant improvement in systolic and diastolic BP in about two thirds and improvement and/or stabilization in renal function in 30-40% of patients undergoing PRA/S. Nevertheless, the issue remains unsolved and a subject of future studies for further more definitive settlement. Suggestions have been made to adopt physiological and functional renal lesion assessment that may enhance patient selection, at least for RAS cases of moderate lesion severity. Based on this small case series and on exhaustive literature review, an algorithm for approaching patients with significant RAS is herein proposed., Conclusion: In high-risk RAS patients with truly resistant hypertension, flash pulmonary edema, and/or rapid deterioration of renal function, PRA/S, a procedure with currently high technical success, may constitute the only viable option. Importantly, despite the unfavorable results of RCTs, current guidelines have not yet changed and clinicians should continue to abide by them. They recommend PRA/S as a reasonable option for patients with hemodynamically significant (especially ostial) RAS and uncontrolled, resistant or malignant hypertension, recurrent, unexplained congestive heart failure or pulmonary edema or unstable angina., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)