The clinical journey of cancer patients is frequently complicated by the development of a complex and multifaceted syndrome, the main features of which are reduced appetite, decreased food intake, progressive weight loss, and wasting of muscle mass and adipose tissue, which is not prevented by the provision of calories and proteins. This syndrome, termed cachexia, is responsible for increased morbidity, reduced survival, and impinged quality of life of cancer patients. The pathogenesis is complex and involves deranged metabolism of peripheral tissues and profound alterations of brain neurochemistry. Recent studies indicate that brain neurochemistry is perturbed during tumor growth by cancer-induced increased intrahypothalamic expression of proinflammatory cytokines. The attending neurochemical chaos mediates the anorexigenic behavioral responses associated to cancer cachexia, but recent data seem to suggest that neuronal output also may be involved in the metabolic changes occurring at the peripheral level. © 2012 by Begell House, Inc.