Abstract Apelin is an adipokine that has been identified as an endogenous ligand for the orphan receptor APJ. Apelin and APJ are expressed in a diverse range of tissues with particular preponderance for the heart and vasculature. Apelin has powerful positive inotropic actions and causes endothelium- and nitric oxide-dependent vasodilatation. Growing evidence shows that apelin/APJ system functions as a critical mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular diseases. Targeting apelin/APJ axis produces protection against cardiovascular diseases. In the current review we have summarized recent data concerning the role and therapeutic potential of apelin/APJ in several major cardiovascular diseases. An increased understanding of the cardiovascular actions of apelin/APJ system will help to develop novel therapeutic interventions for cardiovascular diseases.