Glutathione is the main intracellular defence against oxidative stress and regulates the cellular redox potential. HIV infection is accompanied by severe metabolic and immune dysfunctions. Several laboratories have demonstrated that the intracellular redox balance is disturbed in CD4+ T cells from HIV‐seropositive subjects, which may potentiate HIV replication and partly explain the immunological abnormalities associated with HIV disease. The importance of glutathione for immune function, regulation of gene expression, as well as therapeutic interventions with redox‐active drugs are discussed in this commentary.