In 1981, Bowers reported that xenobiotic peptides, derived from the Leu- and Met- enkephalins, demonstrated novel growth hormone (GH) secretory activity. The most potent peptide reported, GH releasing peptide-6 (GHRP-6), was shown to release GH by a different pathway to the known signalling peptide, growth hormone releasing hormone (GHRH). The discovery of a peptidyl GH secretagogue laid the foundation for the search for smaller, orally active mimetics of GHRP-6, as well as for its mechanism of action. This review focuses on the recent developments in the field of small molecule GH secretagogues from a medicinal chemistry perspective, and discusses various structural classes of mimetics recently reported in the literature.