Despite the many therapeutic options available today for the treatment of hypertension, a large number of patients remain uncontrolled. The classic antihypertensive therapies including β-blockers, diuretics, calcium channel blockers and the wide class of renin–angiotensin–aldosterone system blockers (converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), are variably successful in achieving the target blood pressure values in hypertensive patients. Although these numerous, safe and effective pharmacologic therapies are available to treat hypertension, novel therapeutic approaches are warranted to improve the management and prognosis of patients with this condition. Several lines of research suggest promising results based on novel pharmacologic and device-based approaches that may treat effectively resistant hypertension and target organ damage in the future. A large number of the new therapeutic strategies are related to renin angiotensin aldosterone system (RAAS). Modulation of the RAAS provides the rationale for current new antihypertensive drugs already used in clinical practice, including eplerenone and aliskiren. The combined angiotensin-converting-enzyme and neutral endopeptidase blockade decreases blood pressure, aldosterone synthase inhibitors improve tolerability in aldosterone antagonism, prorenin-receptor blockers could prevent the angiotensin-independent actions of renin. In the past few years new minimally invasive surgical procedures like carotid baroreceptor activation and renal symphatetic denervation were developed and could be a therapeutic option for patients with uncontrolled hypertension.