The sympathetic nervous system has a profound effect on the kidney’s ability to regulate blood pressure and, vice versa, the kidney has an important effect on the overall sympathetic tone. As a result, renal sympathetic nerves are crucial for initiation and the maintenance of systemic hypertension. It is fairly well established that efferent renal sympathetic nerve activity contributes significantly to homeostatic regulation of renal blood flow, glomerular filtration rate, renal tubular epithelial cell solute and water transport, and hormonal release. The afferent nerves from the kidney activate central sympathetic nervous system activity, participate in a reflex control system via reno-renal reflexes and are involved in cardiovascular regulation and pathogenesis of hypertension in CKD patients whose kidney ischemia also seems to play a key role. Sympathetic nerve modulation in hypertension had been considered as a therapeutic strategy long before the advent of modern pharmacological therapies. Renal sympathetic denervation with a percutaneous, catheter-based approach results in significant and sustained blood pressure reduction in patients with resistant hypertension. This procedure has also beneficial effects in multiple organs function. However, renal physiology and the long term observed benefits with the use of renal sympathetic denervation have not completely elucidated.