THE IDENTIFICATION of the ob gene (1) and the discovery that its encoded protein, leptin, is an adipocytederived hormone that is essential for normal regulation of body weight (2–4) have permanently altered the field of metabolic physiology. Over a 3-yr period, more than 800 papers on leptin have been published, creating a substantial and rapidly changing body of knowledge. As often occurs, however, the initial conception of the physiological role of a newly discovered protein requires revision in the light of emerging information. In this paper, I will review the relevant literature and will propose a modified view of leptin’s physiological role. This perspective, although respectful of the profound impact that leptin’s discovery has had upon our understanding of obesity and on the field of obesity research, will attempt to deemphasize the physiological status of leptin as an anti-obesity hormone, stressing instead its roles as a signal of energy deficiency and as an integrator of neuroendocrine function. Although this field is expanding rapidly, and many of these ideas are clearly works in progress, it is hoped that this perspective will be of value to workers in the field.