Apelin is a peptide that has been identified as the endogenous ligand for the receptor APJ. The apelin/APJ system may be an important factor in the regulation of vascular tone and cardiovascular function. Studies on cultured cells and small animal models have revealed that apelin and APJ are localized in cardiomyocytes and vascular cells. The infusion of apelin affects vascular tone and blood pressure, with both central and peripheral actions. In clinical conditions such as heart failure and atherosclerosis, the gene expression of APJ and apelin, as well as the levels of circulating apelin, may be altered. The only known active homolog of ACE, ACE2, hydrolyzes apelin with similar potency to angiotensin II and, therefore, is responsible for the degradation of both peptides. Emerging data on a potential interaction between the two pathways suggest that the function of apelin/APJ in the vasculature may be relevant to cardiovascular disease, and identifying how this system is regulated could be useful clinically.