Oxidative stress has been implicated in various progressive degenerative conditions, such as skeletal muscle wasting and therefore this study sought to determine a role for the superoxide generating NADPH oxidase and antioxidant enzyme systems in conditions of skeletal muscle wasting. The results of these studies indicated changes in the gene expression of important components of NADPH oxidase in animal models of age-associated sarcopenia, cancer-induced cachexia and a model of antioxidant superoxide dismutase overexpression. Also observed were changes in superoxide dismutase that appeared to contribute significantly to alterations in cellular reactive oxygen species and contribute to skeletal muscle wasting in these conditions. While these oxidative and antioxidative systems demonstrated complex changes in these models, NADPH oxidase is indeed altered in response to aging, cancer and superoxide dismutase overexpression, which appear to be involved in complex redox-sensitive signaling that essentially regulates skeletal muscle atrophy and hypertrophy pathways.