The current understanding of appetite and body weight regulation has benefited greatly from the discovery of leptin and advances in the molecular genetics of obesity. Leptin acts as an afferent signal in the brain to suppress appetite and increase energy expenditure. Failure of the leptin feedback system culminates in obesity, diabetes, and a variety of neuroendocrine abnormalities. Energy homeostasis is also influenced by insulin, glucocorticoids, sex steroids, and proinflammatory cytokines. These circulating factors regulate feeding behavior and body weight mainly through the expression of neurotransmitters and peptides in the hypothalamus and various central nervous system regions. By studying the interactions between peripheral signals and central neuronal pathways, researchers hope to gain a better understanding of the pathogenesis of eating disorders, obesity, and associated metabolic disorders.