Glutathione, a cysteine-containing tripeptide, is the most abundant nonprotein thiol in mammalian cells. Glutathione plays an important role in the detoxification of xenobiotic compounds and in the antioxidation of reactive oxygen species and free radicals. Because of its multiple functions in various tissues and its involvement in many diseases and malnutrition, a clear understanding of the interrelationships among tissue glutathione, nutrition, and oxidative stress is clinically relevant. The focus of this review is to discuss the regulation of tissue glutathione concentration by diet and nutritional status, and to apply this information to those diseases and malnutrition in which decreased tissue glutathione and increased oxidative stress are implicated. A potential strategy to rapidly restore glutathione for both antioxidant and immune defense systems before therapeutic treatment in malnourished patients is discussed.Key words: glutathione, dietary regulation, oxidative stress, malnutrition.