Oxidative stress, resulting from mitochondrial dysfunction, excitotoxicity, or neuroinflammation, is implicated in numerous neurodegenerative conditions. Damage due to superoxide, hydroxyl radical, and peroxynitrite has been observed in diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as in acute conditions that lead to neuronal death, such as stroke and epilepsy. Antioxidant therapies to remove these toxic compounds have been of great interest in treating these disorders. Catalytic antioxidants mimic the activities of superoxide dismutase or catalase or both, detoxifying superoxide and hydrogen peroxide, and in some cases, peroxynitrite and other toxic species as well. Several compounds have demonstrated efficacy in in vitro and in animal models of neurodegeneration, leading to optimism that catalytic antioxidants may prove to be useful therapies in human disease.