Accumulating evidence suggests that glucose-dependent insulinotropic polypeptide (GIP) in addition to its involvement in type 2 diabetic pathophysiology may be involved in the development of obesity and the pathogenesis of cardiovascular disease. In this review, we outline recent preclinical and clinical cardiovascular-related discoveries about GIP. These include chronotropic and blood pressure-lowering effects of GIP. Furthermore, GIP has been suggested to control vasodilation via secretion of nitric oxide, and vascular leukocyte adhesion and inflammation via expression and secretion of endothelin 1. Also, GIP seems to regulate circulating lipids via effects on adipose tissue uptake and metabolism of lipids. Lastly, we discuss how dysmetabolic conditions such as obesity and type 2 diabetes may shift the actions of GIP in an atherogenic direction, and we provide a perspective on the therapeutic potential of GIP receptor agonism and antagonism in cardiovascular diseases. We conclude that GIP actions may have implications for the development of cardiovascular disease, but also that the potential of GIP-based drugs for the treatment of cardiovascular disease currently is uncertain.