Multiple sclerosis (MS) is an immune-mediated disease, with inflammation and neurodegeneration contributing to neuronal demyelination and axonal injury. Current therapies for MS are directed toward modulation of the immune response; however, there is increasing evidence that oxidative stress is an important component in the pathogenesis of MS. The inflammatory environment in demyelinating lesions is conducive to the generation of reactive oxygen species. When these species are generated in MS and animal models of MS, products such as peroxynitrite and superoxide are formed that are highly toxic to cells. There are several examples of potential beneficial effects from various antioxidants in animal models of MS, but the efficacy may vary between different agents and, in some instances, may yield deleterious effects. Despite these promising results in animal models, there is limited and conflicting evidence of potential therapeutic effects of antioxidants such as vitamins C and E in treating MS. However, clinical trials in MS patients with more potent antioxidants, identified in animal studies, have been initiated.