Selenium is undoubtedly an essential trace element: its involvement in GPx structure, the presence of deleterious effects of selenium deficiency in animals, and the recognition of deficiency states in man attest to its importance. However, if the consequences of selenium deficiency in man are now widely recognized, the mechanisms underlying these conditions are poorly understood. The definition of the exact role of selenium in human homeostasis has been hampered by the lack of a sensitive parameter, usable in routine investigation, to assess selenium status. Measurements of plasma and urinary levels, although useful in clinical practice, are inadequate indicators. The only true evidence of selenium deficiency lies in a positive response to selenium therapy. Deficiency states have been demonstrated for inhabitants of regions where selenium supply is limited, in protein-energy malnutrition, and in patients maintained on total parenteral nutrition without selenium supplementation. The benefit of selenium supplementation, together with other antioxidant drugs, in non-deficient subjects is still a matter of debate; its protective effect in neoplastic, cardiovascular and neurological degenerative diseases is not yet proven.