Synthesized and released by the adipose tissue, leptin is the widely studied 167-amino acid hormonal protein product of the obesity gene. Originally leptin was defined in association with satiety and energy balance and claimed to be an anti-obesity factor that functioned via a feedback effect from adipocytes to hypothalamus. There is a growing body of evidence that emphasizes the importance of leptin in the regulation of food intake and body weight in animals and humans, alike. Other research findings point out that it plays a role in the regulation of the metabolism, sexual development, reproduction, hematopoiesis, immunity, gastrointestinal functions, sympathetic activation, and angiogenesis. The aim of this review is to evaluate the relation between leptin and the central nervous system (CNS). Copyright (C) 2009 John Wiley & Soils, Ltd.