Obesity, a health problem reaching epidemic proportions in western countries, is an important risk factor for the most frequent diseases in the western world, ie diabetes, hypertension, cardiovascular diseases and certain types of cancer. Thus, significant research efforts have been focusing on its aetiology, prevention and treatment. The recent discovery of leptin (from the Greek word leptos: ie thin), the product of the ob gene (Zhang et al., 1994), has greatly advanced our understanding of body adiposity and energy balance regulation. This hormone, produced mainly by adipose tissue, conveys to the brain information about the size of energy stores and activates hypothalamic centres that regulate energy intake and expenditure (Flier, 1997). Moreover, leptin affects several neuroendocrine mechanisms and regulates multiple hypothalamic–pituitary axes (Flier, 1997). The realization that adipose tissue is not simply a storage depot, but also an important endocrine gland, has created new opportunities for the investigation and, possibly, treatment of diseases such as obesity and eating disorders. In this review, we discuss the biology of leptin secretion and regulation, as well as our current knowledge of the role leptin plays in various physiological and pathophysiological states. Although most available research studies have been based on animal models, a substantial amount of information has been accumulated over the last 3 years on the role of leptin in humans. Thus, this article mainly focuses on our current knowledge about the role of leptin in human physiology and pathophysiology. Finally, some of the important unanswered questions about leptin physiology are discussed and future directions for leptin research are suggested.