Sympathetic nerve activity (SNA) is increased in both patients and experimental animals with renal failure. The kidney is a richly innervated organ and has both efferent and afferent nerves. Renal denervation shows protective effects against renal failure in both animals and humans. The underlying mechanisms include a decrease in blood pressure, a decrease in renal efferent SNA, a decrease in central SNA and sympathetic outflow, and downregulation of the reninangiotensin system. It has been demonstrated that re-innervation occurs within weeks after renal denervation in animals but that no functional re-innervation occurs in humans for over two years after denervation. Renal denervation might not be renal protective in some situations including bile duct ligation-induced renal failure and ischemia/reperfusion-induced acute kidney injury. Catheter-based renal denervation has been applied to patients with both early and end stage renal failure and the published results so far suggest that this procedure is safe and effective at decreasing blood pressure. The effectiveness of renal denervation in improving renal function in patients with renal failure needs to be further investigated.