Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Its main physiological role may be to coordinate the metabolic, endocrine and behavioural responses to starvation. Recent work has identified many factors that regulate leptin production and secretion, including nutrients, hormones and the sympathetic nervous system. Some characteristics of leptin-responsive hypothalamic neurones have now been defined. Other roles for leptin in gut and immune regulation and in foetal development have been proposed. Leptin itself seems ineffective in treating most human obesity, but alternative means of activating appetite-regulatory pathways downstream of leptin are targets for future pharmacological approaches to aid weight loss.