The trace elements copper, zinc and selenium are linked together in cytosolic defense againstreactive oxygen and nitrogen species. Copper, zinc-superoxide dismutase catalyzes the dismutation of superoxide to oxygen and hydrogen peroxide. The latter and other hydroperoxides are subsequently reduced by the selenoenzyme glutathione peroxidase (GPx). Cytosolic GPx can also act as a peroxynitrite reductase. The antioxidative functions of these trace elements are not confined to being constituents of enzymes: 1) copper and zincions may stimulate protective cellular stress-signaling pathways such as the antiapoptotic phosphoinositide-3-kinase/Akt cascade and may stabilize proteins, thereby rendering them less prone to oxidation; and 2) selenium does not only exist in the cell as selenocysteine (as in GPx) but also as selenomethionine, which is regularly present in low amounts in proteins in place of methionine. Selenomethionine catalyzes the reduction of peroxynitrite at the expense of glutathione. Also, low-molecular-weight organoselenium and organotellurium compounds of pharmacologic interest catalyze the reduction of hydroperoxides or peroxynitrite with various cellular reducing equivalents.