Ghrelin is a 28 amino acid peptide, containing a unique octanoyl moiety added post-translationally to Ser3, with diverse activities in the CNS, gastrointestinal tract, and cardiovascular system. In the CNS, ghrelin stimulates release of growth hormone from the anterior pituitary and increases appetite by binding to neurons within the arcuate nucleus. Circulating concentrations of ghrelin increase with preprandially and decrease post-prandially, and thus counterbalances the effects of leptin to coordinate energy balance, appetite and food intake. Ghrelin is also expressed in the cardiovascular system where it acts as a potent vasodilator; receptors are up-regulated in patients with atherosclerosis, suggesting that it plays a role in compensating for increased vasoconstriction. The effects of ghrelin are mediated by a Gq-coupled receptor, originally designated GHSR (growth hormone secretogogue receptor), and more recently termed the Ghrelin Receptor or GRLN. Two splice variants have been described; type 1a (GHS-R1a) is the functional receptor, whereas type 1b (GHS-R1b) encodes a truncated, inactive protein with only 5 transmembrane domains. As administration of agonists of the ghrelin receptor to rats leads to increased food intake and antagonists reduce food intake, antagonism and inverse agonism of the ghrelin receptor may reduce food intake in certain types of obesity, and agonists of the ghrelin receptor are potentially useful for treatment of anorexia and cachexia.