Renal afferent and efferent sympathetic nerves are involved in the regulation of blood pressure and have a pathophysiological role in hypertension. Renal sympathetic denervation is a novel therapeutic technique for the treatment of patients with resistant hypertension. Clinical trials of renal sympathetic denervation have shown significant reductions in blood pressure in these patients. Renal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk. Conditions that are comorbid with hypertension, such as heart failure and myocardial hypertrophy, obstructive sleep apnoea, atrial fibrillation, renal dysfunction, and metabolic syndrome are closely associated with enhanced sympathetic activity. In experimental models and case-control studies, renal denervation has had beneficial effects on these conditions. Renal denervation could become a commonly used procedure to treat resistant hypertension and chronic diseases associated with enhanced sympathetic activation. Current work is focused on refining the techniques and interventional devices to provide safe and effective renal sympathetic denervation. Controlled studies in patients with mild-to-moderate, nonresistant hypertension and comorbid conditions such as heart failure, diabetes mellitus, sleep apnoea, and arrhythmias are needed to investigate the capability of renal sympathetic denervation to improve cardiovascular outcomes.