Our understanding of the regulation of appetite and energy balance has advanced significantly over the past decade as several peptides, centrally or peripherally expressed, have been characterized and shown to profoundly influence food intake and energy expenditure.(1) The growing number of putative appetite-regulating neuropeptides includes peptides that are orexigenic (appetite-stimulating) signals and anorectic peptides. Neuropeptide Y (NPY), melanin concentrating hormone (MCH), orexins A and B, galanin, and agouti-related peptide (AgRP) all act to stimulate feeding while alpha-melanocyte stimulating hormone (alpha MSH), corticotropin releasing hormone (CRH), cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), neurotensin, glucagon-like peptide 1 (GLP 1), and bombesin have anorectic actions.(1) Leptin, expressed in the periphery in white adipose tissue, acts in the CNS to modulate the expression of several of these hypothalamic peptides.(1) This creates a functional link between the adipose tissue and the brain that translates the information on body fat provided by leptin to input into energy balance regulating processes. In the current review we examine the significant role of the melanocortin system (alpha MSH, agouti and AgRP peptides, and their receptors and mahogany protein) and melanin concentrating hormone in the regulation of energy balance. (C) 1999 Harcourt Publishers Ltd.