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Until few years ago it was generally accepted that the secretion of growth hormone (GH) was mainly regulated by stimulatory and inhibitory influences of two hypothalamic hypophysiotropic hormones, the growth hormone releasing hormone (GHRH) and somatostatin (SS), respectively. GHRH and SS were considered the final common pathway by which neurotransmitters, peripheral hormone, and environmental, metabolic and immune stimuli could influence the secretion of GH (Locatelli and Torsello, 1997; Muller et al., 1999). However, at the end of 1970s, the observation that several synthetic peptidyl and non-peptidyl molecules, derived from the pentapeptide met-enkephalin and named “growth hormone secretagogues” (GHS), were able to potently stimulate GH secretion from cultured pituitary cells (Bowers et al., 1980), experimental animals (Bowers et al., 1984), and humans (Ilson et al., 1989; Bowers et al., 1990) was suggestive of the existence of another endogenous factor physiologically involved in the regulation of GH release. In 1996, the identification of a specific GHS receptor (GHS-R) distinct from that of GHRH (Howard et al., 1996; Pong et al., 1996) further supported this hypothesis, and made possible the recent discovery of its endogenous agonist. The endogenous natural ligand of the GHS-R was isolated from a peripheral tissue, the stomach, and not, as generally expected, from the hypothalamus, and was named “ghrelin” (ghre is the Proto-Indo-European root of the word “grow”) (Kojima et al., 1999).