Unacylated ghrelin (UAG), or des-acyl ghrelin, is slowly fighting its way up into the field of interest that studies preproghrelin gene-encoded peptides. Long considered to be an inert degradation product of (acylated) ghrelin (AG), UAG nowadays emerges as an important hormone, separate from the other proghrelin-derived peptides, AG and obestatin. UAG appears to have its own receptor, and it can share this receptor with AG, under experimental conditions at least. An increasing number of studies suggest that UAG can act as a potent functional inhibitor of ghrelin. It can even strongly suppress ghrelin levels in obese human diabetic subjects. Moreover, UAG can improve postprandial glycemia, especially in those subjects in whom preprandial acylated ghrelin levels are high, which makes UAG, or UAG analogs strong potential candidates for the development of drugs for the treatment of metabolic disorders or other conditions in which elevated AG/UAG ratios occur, such as diabetes, obesity and Prader-Willi syndrome. Copyright