Hypertension represents a major health problem, with an appalling annual toll. Despite the plethora of antihypertensive drugs, hypertension remains resistant in a considerable number of patients, thus creating the need for alternative strategies, including interventional approaches. Recently, renal sympathetic denervation (RSD) using a very elegant, state-of-the-art technique (percutaneous, catheter-based radiofrequency ablation) was shown to be beneficial in patients with resistant hypertension. The pathophysiology of kidney function justifies the use of RSD in the treatment of hypertension. Data from older studies have shown that sympathectomy has efficiently lowered blood pressure and prolonged the life expectancy of patients with hypertension, but at considerable cost. RSD is devoid of the adverse effects of sympathectomy because of its localized nature, is minimally invasive, and provides short procedural and recovery times. In conclusion, this review outlines the pathophysiologic background of RSD, describes the past and the present of this interventional approach, and considers several future potential applications.