During the 1970s and 1980s, many gut peptides (ie, cholecystokinin, bombesin, gastrin-releasing peptide, neuromedin B, glucagon) were linked to satiety. During the 1990s, leptin was recognized as a long-term adiposity signal that regulated food intake. In 1999, ghrelin (a 28 amino acid acyl-peptide) was first described by Kojima et al1 as the endogenous ligand to the receptor for growth hormone secretagogues, a group of molecules endowed with growth hormone-releasing activity. Ghrelin also serves as a peripheral signal from the stomach to the brain, informing the brain about gastric nutrient content. The primary sites of ghrelin action within the brain are the pituitary and hypothalamus. Ghrelin is synthesized primarily in enterochromaffin cells located mainly in the fundus of the stomach. Ghrelin secretion is increased by an empty stomach and signals the brain to increase food intake and release growth hormone. Stimulation of food intake by ghrelin is mediated via neuropeptide Y neurons in the hypothalamus. Due to its role in the regulation of food intake, much of the research on ghrelin relates to obesity. However, ghrelin may also play significant roles in wasting syndromes, such as occurs in patients with COPD. In these states, ghrelin may stimulate food intake while decreasing fat oxidation. In humans, circulating ghrelin levels are decreased in acute states of positive energy balance such as obesity and are increased during fasting and starvation.