The discovery of the adipocyte-produced hormone leptin has greatly changed the field of obesity research and our understanding of energy homeostasis. It is now accepted that leptin is the afferent loop informing the hypothalamus about the state of fat stores, with hypothalamic efferents regulating appetite and energy expenditure. In addition, leptin has a role as a metabolic adaptator in overweight and fasting states. New and previously unsuspected neuroendocrine roles have emerged for leptin. In reproduction, leptin is implicated in fertility regulation, and it is a permissive factor for puberty. Relevant gender-based differences in leptin levels exist, with higher levels in women at birth, which persist throughout life. In adult life, there is experimental evidence that leptin is a permissive factor for the ovarian cycle, with a regulatory role exerted at the hypothalamic, pituitary, and gonadal levels, and with unexplained changes in pregnancy and postpartum. Leptin is present in human milk and may play a role in the adaptive responses of the newborn. Leptin plays a role in the neuroendocrine control of GH secretion, through a complex interaction at hypothalamic levels with GHRH and somatostatin. Leptin participates in the expression of CRH in the hypothalamus, interacts at the adrenal level with ACTH, and is regulated by glucocorticoids. Since leptin and cortisol show an inverse circadian rhythm, it has been suggested that a regulatory feedback is present. Finally, regulatory actions on TRH-TSH and PRL secretion have been found. Thus leptin reports the state of fat stores to the hypothalamus and other neuroendocrine areas, and the neuroendocrine systems adapt their function to the current status of energy homeostasis and fat stores.