Oxidative stress occurs as a consequence of an alteration in the equilibrium of the production of reactive oxygen species and antioxidative processes in favor of the production of reactive oxygen species. Such compounds are continuously generated during oxidative metabolism. Compared to other organs the brain appears to be in an unfavorable position regarding the generation and the detoxification of reactive oxygen species. Evidence for the occurrence of oxidative stress in brain has been reported for aging and a variety of neurological and neurodegenerative diseases, indicating that under such conditions antioxidative processes, such as the glutathione system, might be insufficient. The following two minireviews summarize the current knowledge on the metabolism of the antioxidant glutathione in brain cells and the evidence for disturbances of the metabolism of this antioxidant under neuropathological conditions. Recent evidence for a metabolic cooperation between astrocytes and neurons in glutathione metabolism has enhanced the knowledge of the basal metabolism of this antioxidant in brain and suggests new strategies for potential prevention of neuronal loss during oxidative stress in brain.