SNS (sympathetic nervous system) activation is a common feature of arterial hypertension and hasbeen demonstrated to contribute to the development and progression of the hypertensive state. Persuasive evidence suggests a strong association between SNS overactivity and variety of disease states, including chronic renal failure, insulin resistance, congestive heart failure, sleep apnoea, ventricular arrhythmias and others. Although sympatholytic agents are available to target SNS overactivity pharmacologically, they are not widely used in clinical practice, leaving the SNS unopposed in many patients. The recent introduction of catheter-based renal denervation as an alternative approach to targetthe SNS therapeutically has been demonstrated to result in a clinically relevant blood pressure reduction in patients with resistant hypertension, presumably through its effects on both efferent and afferent renal nerve traffic. Available data on this interventional procedure demonstrate a favourable vascular and renal safety profile. Preliminary data obtained primarily from small and mostly uncontrolled studies in related disease states often characterized by overactivity of the SNS are promising, but require confirmation in appropriately designed clinical trials. In the present paper, we briefly review the physiology of the renal nerves and their role in hypertension and other relevant disease states, summarize the data currently available from clinical studies pertaining to the safety and efficacy of renal denervation in resistant hypertension, discuss potential future implications and the available data supporting such a role for renal denervation, and describe some of the newer devices currently under investigation to achieve improved blood pressure control via renal denervation.