Resistant hypertension is a common and growing clinical problem characterized by failure to achieve target blood pressure levels despite adequate use of at least three antihypertensive agents. Although numerous safe and effective pharmacologic therapies are available to treat elevated blood pressure, novel therapeutic approaches are warranted to improve the management and prognosis of patients with resistant hypertension. In this context, several lines of research have generated promising results based on both novel pharmacologic and device-based approaches that may more effectively treat resistant hypertension and its adverse consequences in the future.