Multiple mechanisms are involved in essential hypertension. Antihypertensive drugs mainly target increased activity of the sympathetic nervous system, altered production of vasoactive mediators, vascular inflammation, fibrosis, and increased peripheral resistance. C-type natriuretic peptide (CNP) is an endothelium-derived peptide that exerts vascular signaling through two receptors: natriuretic peptide receptor-B (NPR-B) and natriuretic peptide receptor-C (NPR-C). This perspective recapitulates the effects of CNP on the vasculature in relation to essential hypertension. Notably, the risk of hypotension when used as therapy is minimal for the CNP system as compared to its related natriuretic peptides, atrial natriuretic peptide, and B-type natriuretic peptide. As modified CNP is currently being introduced as therapy in congenital growth disorders, we propose that targeting the CNP system either by administering exogenous CNP or altering the endogenous concentrations via inhibition of its degradation may represent an important tool in the pharmacological armory for managing long-term essential hypertension.