Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent advances in leptin physiology have revealed that the main role of this hormone in humans is to signal energy availability in energy-deficient states. Interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. Moreover, recent "proof of concept" studies involving leptin administration to humans further support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/caloric deprivation. Leptin's potential role in the therapy of several disease states, including hypothalamic amenorrhea, anorexia nervosa and syndromes of insulin resistance is under intensive investigation.