Energy homeostasis is tightly controlled via hormonal signals communicating the energy state of peripheral tissues to the central nervous system. It has been demonstrated that insulin provides such a signal rising both short-term in response to increased blood glucose concentrations and long-term in correlation with body fat stores. Insulin receptors are widely expressed across the central nervous system with the highest density in hypothalamic areas responsible for the regulation of food intake and energy expenditure. Moreover, peripherally administered insulin is capable of crossing the blood/brain barrier to act on these receptors. Insulins ability to inhibit food intake and to increase energy expenditure appears to be regulated via a neuronal network in the arcuate nucleus of the hypothalamus involving both the regulation of the melanocortin pathway as well as neurons expressing neuropeptide Y in the agouti-related peptide. The presentation will focus on the genetic determination of the anatomical sites in the central nervous system and signal transduction pathways targeted by insulin.