Vascular dysfunction is an important hallmark of cardiovascular disease. It is characterized by increased sensitivity to vasoconstrictors, decreases in the endothelium-derived vasodilators nitric oxide (NO) and prostacyclin (PGI2), and endothelium-derived hyperpolarization (EDH). Serelaxin (recombinant human relaxin) has gained considerable attention as a new vasoactive drug, largely through its beneficial therapeutic effects in acute heart failure. In this review we first describe the contribution of endogenous relaxin to vascular homeostasis. We then provide a comprehensive overview of the novel mechanisms of serelaxin action in blood vessels that differentiate it from other vasodilator drugs and explain how this peptide could be used more widely as a therapeutic to alleviate vascular dysfunction in several cardiovascular diseases.