Appetite and energy balance are controlled by a multicomponent regulatory system co-ordinated by the brain, to achieve a balance between energy expenditure and food intake. Within the brain the area known as the hypothalamus plays a key role. Several of the most important neuropeptides involved in appetite and energy balance are synthesised in a number of nuclei that constitute this region including, orexigenic NPY and MCH peptides or anorexigenic α-MSH and TRH. Nuclei of the hypothalamus also receive many signals from hormones that play a role in appetite and energy balance including hormones from peripheral tissues, such as leptin (anorexigenic) from fat, insulin (anorexigenic) from pancreas and ghrelin (orexigenic) from the stomach. Many signals are also received via afferent neuronal inputs from regions of the brain outside the hypothalamus, including the hind brain and other forebrain nuclei. It is the balance between the orexigenic and anorexigenic signals that will determine energy expenditure and food intake. In all, using animal models whose appetite or energy expenditure has been manipulated by diet, pharmacology, or photoperiodelled.ar and cellular mechanisms that drive us to eat when hungry or drive us to eat even when we are not hungry are being or by engineered or natural gene mutations, the complexity of co-ordinating signals arising from peripheral tissues and internally within the brain, is slowly, but surely being unravelled at the molecular and cellular level to define vle unravelled atmechanisms that drive us to eat when hungry or drive us to eat even when we are not hungry.