Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure. © Springer Science+Business Media, LLC 2012.