Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most but not all device-based treatments target the sympathetic nervous system and provided important new insight in the mechanisms of human hypertension. This review provides an overview on the scientific rational and clinical data on recent device-based antihypertensive treatment approaches. Device-based treatments targeting the sympathetic nervous system include catheter-based renal nerve ablation, electrical carotid sinus stimulation, modulation of baroreflex transduction through a dedicated carotid stent, carotid body denervation, and deep brain stimulation. Creation of a defined arteriovenous stent with a coupler device and removal of stimulatory antibodies against alpha adrenoreceptors have also been tested. The clinical evidence differs from therapy to therapy with the largest dataset for renal nerve ablation followed by electrical carotid sinus stimulation. Yet, none has been proven efficacious in sham-controlled clinical trials, and none has been shown to reduce cardiovascular morbidity or mortality. Before efficacy is proven, these treatments should not be part of routine medical care and only be applied in the setting of clinical studies.