Ghrelin is a gut-brain peptide that has somatotropic, food intake increasing and adipogenic effects. Ghrelin is involved in modulating insulin and glucose metabolism in rodents according to recent studies. In humans acylated ghrelin reduces insulin sensitivity while unacylated ghrelin has opposite effects. In general, ghrelin seems to have diabetogenic effects. Obese, in particular abdominally obese, subjects have low ghrelin levels and decreased total ghrelin levels have been associated with metabolic syndrome and Type 2 diabetes. Most of the human studies in Type 1 diabetes have reported low ghrelin levels probably as a compensatory mechanism against hyperglycaemia. The data on obestatin in the regulation of energy balance is extremely contradictory. Interestingly, ghrelin receptor antagonists may improve glucose tolerance in rats without inducing weight gain by increasing insulin secretion. Antagonism of ghrelin function to treat diabetes is thus a fascinating idea. This review concentrates on recent findings on the orexigenic peptide ghrelin and its derivatives in metabolic disorders with emphasis put on human studies.