The concept of targeting the renal sympathetic nerves therapeutically to lower blood pressure (BP) is based on their crucial role in regulating both renal and cardiovascular control. These effects are mainly mediated via three major mechanisms including alteration of renal blood flow, renin-release, and Na retention. Initial surgical approaches applying crude and unselected sympathectomy, while rendering significant BP lowering and cardiovascular event reducing properties, where plagued by side effects. More modern selective catheter-based denervation approaches selectively targeting the renal nerves have been shown to be safe and effective in reducing BP in various forms of hypertension and multiple comorbidities.+This article covers the background relevant for the concept of renal denervation (RDN), the evidence obtained from relevant randomized controlled trials to substantiate the safety and efficacy of RDN, and recently published clinical recommendations.Catheter-based RDN is safe and has now been shown in sham-controlled randomized clinical trials to result in clinically meaningful BP lowering in both drug naïve hypertensive patients and those on concomitant antihypertensive therapy. Real world data from a large global registry further supports the clinical utility of RDN. It now seems time to embed renal denervation into routine clinical care.