Hypertension affects more than one-fourth of the adult population worldwide and is a major risk factor for cardiovascular and kidney disease. Currently, the majority of patients with hypertension do not reach goal blood pressure (BP) targets, and cardiovascular risk is increased further for patients with treatment-resistant hypertension, defined as office BP above goal despite pharmacological treatment with three or more antihypertensive medications at optimal doses including a diuretic. Although missed diagnosis of secondary forms of hypertension, physician inertia and non-adherence with prescribed medication are important contributors to the phenomenon of resistant hypertension that need to be addressed, there is a need for alternative therapeutic approaches. Renal sympathetic denervation is a minimally invasive endovascular procedure that disrupts renal efferent and afferent neural connections, both of which are important regulators of BP control. Limited data from recent clinical trials indicate that this approach is safe and effectively lowers BP in patients with treatment-resistant hypertension. Accumulating data is emerging to suggest that renal sympathetic denervation may also have utility beyond treatment-resistant hypertension. This review aims to briefly summarize the existing evidence for the use of renal denervation (RDN) in patients with treatment-resistant hypertension and to explore the potential utility of RDN in other pathological states associated with sympathetic dysfunction.