The sympathetic nervous system via its effect on the kidney maintains a key role in blood pressure regulation and in the pathogenesis of hypertension. In turn, the kidney receives a dense innervation of afferent sympathetic fibers allowing it to effectively modulate the sympathetic tone. Hence, the kidney can be both culprit and victim of increased sympathetic activity. In addition, conditions such as congestive heart failure, chronic renal failure or the metabolic syndrome are associated with an increased sympathetic activity whether or not hypertension is present. On this account, both the sympathetic nervous system and the kidney were identified as potential therapeutic targets in the treatment of hypertension and other conditions associated with a high sympathetic tone. Initial investigations focused on surgical removal of the sympathetic trunk, unfortunately accompanied by operative mortality and major side effects. More specific methods of disrupting interactions between the sympathetic nervous system and the kidneys were subsequently explored including the removal of diseased kidneys and, more recently, minimally invasive severance of the renal sympathetic nerves. Currently, most hypertensive patients can be treated by effective antihypertensive drugs. Notwithstanding, a small group of hypertensive patients remains suboptimally controlled despite identification of potential causes and appropriate treatment. In this group an elevated sympathetic tone may be a significant contributor to treatment resistance and selective renal sympathectomy may be beneficial. The role of the sympathetic nervous system in blood pressure control and the effect of selective sympathectomy are discussed in this review.