Reactive oxygen metabolites generated during normal metabolism and metabolism stimulated by xenobiotics can enter into reactions that, when uncontrolled, can impair performance of dairy cows. Direct effects include peroxidative changes in membranes and other cellular components. Indirectly, competitive consumption of reducing equivalents can interfere with important metabolic functions and divert glucose from other pathways by inducing the monophosphate shunt. Normally, the body is protected by a wide range of antioxidant systems working in concert. Metal catalysts of oxidative reactions are removed in intracellular fluids by metal-binding macromolecules. Superoxide dismutases, glutathione peroxidase, and catalase within cells remove superoxide and peroxides before they react with metal catalysis to form more reactive species. Finally, peroxidative chain reactions initiated by reactive species that escaped enzymatic degradation are terminated by chain-breaking antioxidants, including water-soluble ascorbate, glutathione, and urate and lipid-soluble vitamin E, ubiquinone, and beta-carotene. To optimize performance, oxidative stress in high producing cows must be controlled by supplying all known antioxidant nutrients and by minimizing effects of substances that stimulate reactive oxygen metabolites.