This literature review provides insights into how glutathione (GSH) plays an important role in controlling HIV-1 and Mycobacterium tuberculosis infections. Since the discovery of HIV in 1981, >40 million affected individuals have died due to AIDS, and currently 40 million people are infected with HIV worldwide, which primarily infects CD4+ T cells. The natural pathogenesis of HIV consists of three stages: 1) the primary HIV infection phase, 2) the asymptomatic chronic phase, and 3) the late HIV symptomatic phase, which leads to an immunocompromised state resulting in increased susceptibility to opportunistic infections. It has been shown that HIV+ individuals have low levels of GSH; increased levels of proinflammatory cytokines, which correlate with increased production of reactive oxygen species and oxidative stress; and increased levels of TGF-β compared to healthy individuals. Consequently, increased reactive oxygen species levels lead to decreased levels of reduced GSH and increased levels of TGF-β, which has been demonstrated to inhibit the rate-limiting enzyme responsible for the de novo synthesis of GSH. In addition, the authors demonstrate that with supplementation of reduced GSH, there is improved intracellular control of an M. tuberculosis infection within macrophages. Therefore, decreased levels of GSH can leave HIV+ individuals prone to such opportunistic infections. The HIV transactivator of transcription (TAT) protein has also been shown to further increase oxidative stress and reduce GSH levels. Liposomal-GSH supplementation has the ability to bypass de novo GSH synthesis and provide protection against HIV and M. tuberculosis infections by increasing levels of GSH, improving redox homeostasis, and dampening the effects of TGF-β.