Lowering blood pressure by pharmacologic intervention reduces the incidence of cardiovascular events. Nevertheless, despite the widespread availability of effective antihypertensive medications, the vast majority of hypertensive patients worldwide continue to have inadequate blood pressure control. The development of new antihypertensive drugs could contribute to improving the hypertension control rate, and the blockade of new pathophysiologic pathways involved in blood pressure regulation would offer additional benefits. The dual inhibition of the angiotensin II receptor and neprilysin could provide clinical benefits in a range of cardiovascular diseases, including hypertension and heart failure.