Ghrelin, a 28-amino acid acylated peptide produced predominantly by the stomach, displays strong growth hormone (GH)-releasing activity via the hypothalamus-pituitary GH secretagogue (GHS) receptors that are specific for synthetic GHSs. Ghrelin's discovery changed our understanding of GH regulation. Evidence indicates that ghrelin also acts on other central and peripheral receptors and has other actions, including stimulation of lactotroph and corticotroph secretion; effects on gastroenteropancreatic functions; and orexigenic, metabolic, cardiovascular, and antiproliferative effects. When GHSs were developed more than 20 years ago as synthetic molecules, it was suggested that orally active GHSs might serve as alternatives to recombinant human GH for the treatment of GH deficiency. This proved not to be the case, however, and their utility as anabolic anti-aging agents to restore the GH-insulin-like growth factor-I axis during somatopause remains unclear. There is today, however, the possibility that GHS analogues could become candidate drugs for the treatment of conditions unrelated to disorders of GH secretion.