The discovery of ghrelin has elucidated the role of the stomach as an important organ in the regulation of growth hormone (GH) release and energy homeostasis. Ghrelin is a peptide hormone in which Ser3 Thr3 in frogs) is modified by an n-octanoic acid; this modification is essential for ghrelin's activity. Ghrelin and motilin, another gastric peptide, structurally and functionally define a peptide superfamily; these two factors may have evolved from a common ancestral peptide. Ghrelin is found in both mammalian species as well as nonmammalian species, such as frogs, birds, and fish. Moreover, ghrelin structure, particularly that of the acyl-modification regions, is highly conserved throughout vertebrate species. All of the ghrelin peptides that have been identified are modified by a fatty acid, primarily n-octanoic acid. These discoveries implicate ghrelin as an essential hormone in the maintenance of GH release and energy homeostasis in vertebrates.