Apart from promoting GH secretion and to regulate appetite and metabolism, it has become increasingly clear that GH secretagogues (GHS) and ghrelin exert a number of effects on the cardiovascular system. The main cardiovascular actions of GHS are possible inotropic effects, vasodilation, reported cardioprotective effects against ischemia, and in vitro effects on cardiomyocytes involving cell proliferation and anti-apoptotic actions. An interesting and intriguing feature of the cardiovascular effects of GHS is that they may be exerted directly on the heart and vasculature rather than being mediated by growth hormone. Evidence to suggest this is the finding of GHS binding sites on cardiomyocytes and the fact that some of the effects of GHS can be expressed also in the absence of GH. Taken together, these results offer an interesting perspective on the future where further studies aiming at evaluating a role of GHS and ghrelin in the treatment of cardiovascular disease are warranted.