Abstract : Sepsis is characterized by severe redox imbalance. Glutathione plays a major role in cellular defenses against oxidative and nitrosative stress. This review proposes a critical analysis of available data on potential factors affecting glutathione synthesis in sepsis. Glutathione is synthesized from its constituent amino acids—glutamate, cysteine, and glycine. Cysteine availability and the activity of the enzyme glutamate cysteine ligase are rate-limiting for glutathione synthesis. Neutrophils have a dual role in sepsis—defending against infection and mediating organ failure. Because glutathione (GSH) is lower in sepsis, the hypothesis that GSH depletion might impair the migratory response of neutrophils to infection. GSH depletion inhibits neutrophil infiltration, increases bacterial colonies. Conversely, the GSH and its precursor N-acetyl-L-cysteine augments neutrophil infiltration, decreases bacterial colonies and improves survival. Thus, migration of neutrophils to a site of infection and to a distant site is differently regulated, and optimal GSH levels are important for an efficient response to sepsis.