Recent major breakthroughs in our understanding of the negative feedback control of body weight have modified our understanding of disorders characterized by both too much and too little body fat. On the one hand, defective negative feedback signalling in the form of leptin contributes to certain forms of obesity, at least in rodent models. On the other, excessive leptin-like signalling, potentially resulting from the elaboration of inflammatory cytokines, may contribute to the pathogenesis of wasting illness. With the rapid pace of progress that has occurred in this field in recent years, it seems likely that breakthroughs in the treatment of these catastrophic illnesses may follow in the wake of new insights into the physiology and pathophysiology of body weight regulation.