Despite the availability of effective antihypertensive therapies, rates of global blood pressure control are low. Contributing factors include low adherence to treatment, therapeutic inertia, and increasing multimorbidity. These circumstances highlight the need for innovative approaches to improve hypertension care. New antihypertensive drug therapies are emerging that act on physiological pathways outside of conventional drug classes. These include small interfering RNA agents, inhibiting angiotensinogen synthesis as a new way to block the renin-angiotensin system. Other strategies include more selective modulation of aldosterone through aldosterone synthase inhibitors and nonsteroidal mineralocorticoid receptor antagonists.