In recent years, catheter-based radiofrequency denervation of the renal arteries (RDN) has emerged as a potential treatment for resistant hypertension. Though initial non-randomized and randomized small studies demonstrate large reductions in office blood pressure, RDN superiority to conventional treatment is not confirmed either by randomized controlled trials or by large international registries. Increasing evidence supports the hypothesis that a rational pharmacological therapeutic scheme is equally or more effective; this approach, together with an intervention aimed at increasing patient’s compliance with treatment, might solve most of the cases of refractory hypertension. Thus, based on current evidence, renal denervation should not be routinely used to treat resistant hypertension. Though the possibility that RDN might be useful in other subsets of hypertensive patients exists, it has never been proven. Thus, its use should be limited to extreme situations, when all other possible treatments have failed.