Cachexia or wasting disease occurs commonly in diseases that have an overproduction of proinflammatory cytokines associated with them. The hallmarks of cachexia are loss of lean and adipose tissue, anorexia, anemia, memory disturbance, and sickness behavior. This review suggests that increased inducible nitric oxide synthase production in the hypothalamus leads to severe anorexia and that this is the pathway through which proinflammatory cytokines produce anorexia. Orexigenic peptides, such as neuropeptide, ghrelin, and orexin A, and anorectic peptides, such as leptin, produce their effects through neuronal nitric oxide synthase. Activation of neuronal nitric oxide synthase results in increased adenosine monophosphate kinase and a decrease in malonyl coenzyme A, leading to increased food intake.