Cytokine immunotherapy with interferon-alpha, interleukin-1, interleukin-2, or tumor necrosis factor-alpha is consistently associated with anorexia and other neurologic and neuropsychiatric manifestations. Preclinical and clinical studies have shown that cytokines induce anorexia when administered peripherally or into the brain. Cytokine-induced anorexia involves both peripheral and central nervous system mechanisms. Cytokines modulate gastrointestinal activities, cause metabolic changes, affect the endocrine system, and modulate the normal neurotransmitter/neuropeptide profile of the hypothalamus, all of which can influence eating behavior. The direct effects of interferon-alpha, interleukin-1beta, and tumor necrosis factor-alpha on glucose-sensitive neurons in two specific regions of the hypothalamus could cause profound changes in eating patterns in animals and humans. Cytokine immunotherapy also induces production of a large array of endogenous cytokines, which may act synergistically to cause anorexia, taste aversions, and other neuropsychiatric manifestations. A variety of approaches have been proposed for ameliorating cytokine-induced anorexia. These include dietary supplementation with specific fatty acids, megestrol acetate, and specific neuropeptides or peptide hormones that have the ability to modulate cytokine production or activity.