Severe hypertension, resistant to conventional antihypertensive medications, is associated with major adverse cardiovascular and cerebrovascular events and renal insufficiency. Renal sympathetic nerve over-activity frequently accompanies essential hypertension. Catheter-based renal sympathetic denervation leads to a reduction in renal and overall sympathetic nerve activity and improvement in blood pressure in the setting of severe resistant hypertension. In the following, we review the role of the renal sympathetic nervous system in blood pressure control and recent clinical experience with renal denervation. Furthermore, potential beneficial effects on diabetes control, obstructive sleep apnea, atrial and ventricular arrhythmias are discussed.