The discovery of the adipocyte-produced hormone leptin has greatly changed the field of obesity research and future treatment as well as our understanding of energy homeostasis in man. In addition to its relevant role as a metabolic adaptor to overweight and fasting states, new and previously unsuspected neuroendocrinological roles have emerged for leptin. In reproduction, leptin is implicated in fertility regulation and appears as a permissive factor for puberty. In particular, various sets of data suggest that leptin may serve as a signal to the central nervous system (CNS) with information on the critical amount of adipose tissue stores that is necessary for gonadotropin-releasing hormone (GnRH) secretion and pubertal activation of the hypothalamic-pituitary-gonadal axis. Leptin also acts at the periphery, directly on the ovary and testis where it may control steroidogenesis, although the exact role of intragonadal action in the physiology and pathophysiology of the human reproductive system needs to be further elucidated. Furthermore, relevant gender-based differences in leptin levels exist, with higher levels in women, even at birth, and which persist throughout life. In adult life, there is experimental evidence that leptin is a permissive factor for the menstrual cycle, with a regulatory role exerted at hypothalamic, pituitary and gonadal levels, and with severe changes in pregnancy and postpartum. Moreover, leptin is present in both human and commercial milk, and may play a role in the adaptive responses of the newborn.