Apelin is a neuropeptide expressed in the supraoptic and paraventricular nuclei and is an endogenous ligand for APJ, a G protein-coupled orphan receptor which is an alternative coreceptor with CD4 for HIV-1. Apelin and APJ are ubiquitously expressed in peripheral tissues, with highest levels reported for heart and lungs, as well several regions within the central nervous system. The actions of apelin remain largely unknown: Apelin inhibits HIV-1 entry in cells coexpressing CD4 and APJ; the oral intake of Apelin in colostrum and breast milk could have a role in the modulation of the immune responses in neonates; more recent studies have also indicated a role for Apelin in the central control of body fluid homeostasis, by influencing AVP release and drinking behavior. In the cardiovascular system several actions of Apelin have been described, including endothelium-dependent vasodilatation, vasoconstriction through direct action on smooth muscle and positive inotropism.