Anorexia is associated with disorders of all systems. Anorexia represents a consistent clinical manifestation during acute and chronic pathophysiological processes (infection, inflammation, injury, toxins, immunological reactions, malignancy and necrosis). Anorexia during disease can be beneficial or deleterious depending on the timing and duration. Temporary anorexia during acute disease may be beneficial to an organism since a restriction in the intake of micro- and macro-nutrients will inhibit bacterial growth. Long-term anorexia during chronic disease, however, is deleterious to an organism and may be associated with cachexia, which can ultimately result in death. Various mechanisms participate in the anorexia observed during disease, including cytokine action. Anorexia induced by cytokines is proposed to involve modulation of hypothalamic-feeding associated sites, prostaglandin-dependent mechanisms, modifications of neurotransmitter systems, gastrointestinal, metabolic, and endocrine factors. In addition, the anorexia-cachexia syndrome is multifactorial and may involve chronic pain, depression or anxiety, hypogeusia and hyposmia, chronic nausea, early satiety, malfunction of the gastrointestinal system, metabolic alterations, cytokine action, production of other anorexigenic substances and/or iatrogenic causes (chemotherapy, radiotherapy). Cachexia may result not only from anorexia and a decreased caloric intake, but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions), or a change in body metabolism. Research has focused on potential interventions to modify anorexia during disease and the anorexia-cachexia syndrome. Nutritional modifications and the use of specific steroids (such as megestrol acetate) are being tested in the clinical setting. Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexia (during a critical time in a specific disease), and to devise less toxic immunotherapeutic regimens using cytokines.