 Glutathione, GSH, is a redox-active thiol that serves as a cofactor for antioxidant and detoxifying enzymes in cells, and its distribution in different compartments, including mitochondria, plays a key role in defense against reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Mitochondrial GSH regulates cell death and prevalent human diseases such as cancer, fatty liver disease, and Alzheimer's disease. This article was authored by Vicent Iribis, Carmen Egar Siruiz, and Jose C. E. Fernandez Checa.