Cellular oxidants include a variety of reactive oxygen, nitrogen, and chlorinating species. It is well established that the increase in metabolic rate in skeletal muscle during contractile activity results in an increased production of oxidants. Failure to remove these oxidants during exercise can result in significant oxidative damage of cellular biomolecules. Fortunately, regular endurance exercise results in adaptations in the skeletal muscle antioxidant capacity, which protects myocytes against the deleterious effects of oxidants and prevents extensive cellular damage. This review discusses the effects of chronic exercise on the up-regulation of both antioxidant enzymes and the glutathione antioxidant defense system. Primary antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase will be discussed as well as glutathione, which is an important nonenzymatic antioxidant. Growing evidence indicates that exercise training results in an elevation in the activities of both superoxide dismutase and glutathione peroxidase along with increased cellular concentrations of glutathione in skeletal muscles. It seems plausible that increased cellular concentrations of these antioxidants will reduce the risk of cellular injury, improve performance, and delay muscle fatigue.