Despite the availability of multiple antihypertensive drugs targeting the different pathways implicated in its pathophysiology, hypertension remains poorly controlled worldwide, and its prevalence is increasing because of the aging of the population and the obesity epidemic. Although nonadherence to treatment contributes to uncontrolled hypertension, it is likely that not all the pathophysiological mechanisms are neutralized by the various classes of antihypertensive treatment currently available, and, the counter-regulatory mechanisms triggered by these treatments may decrease their blood pressure-lowering effect. The development of new antihypertensive drugs acting on new targets, with different modes of action, therefore, remains essential, to improve blood pressure control and reduce the residual burden of cardiovascular risks further. However, the difficulties encountered in the conception, development, costs, and delivery to the market of new classes of antihypertensive agents highlights the hurdles that must be overcome to release and to evaluate their long-term safety and efficacy for hypertension only, especially because of the market pressure of cheap generic drugs. New chemical entities with blood pressure-lowering efficacy are thus being developed more for heart failure or diabetic kidney disease, 2 diseases pathophysiologically associated with hypertension. These include dual angiotensin II receptor-neprilysin inhibitors, soluble guanylate cyclase stimulators, nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists, as well as sodium-glucose cotransporter 2 inhibitors. However, centrally acting aminopeptidase A inhibitors and endothelin receptor antagonists have a dedicated program of development for hypertension. All these emergent drug classes and their potential use in hypertension are reviewed here.