Hypertension refractory to conventional management with medication remains a significant cause of cardiovascular morbidity and mortality. Alternative strategies are warranted in this subgroup of patients. The target of these strategies centers around sympathetic neural activity, which is thought to play a key role in hypertension. We will review the historic and current approaches toward altering sympathetic neural activity, specifically discussing surgical sympathectomy, catheter-based renal denervation strategies, and baroreflex activation therapy.