Context • Oxidative stress and tissue-damaging, oxygen (O2)-related, free-radical formation is inherent in human metabolism, and the tissues of the ear, nose, and throat (ENT) have an increased exposure to injury from those substances. Because glutathione (GSH) is a major component in an antioxidant defense against oxidative damage in ENT tissues, a review of the impact of lowered GSH and oxidative stress in conditions associated with the upper respiratory tract is warranted. Objective • The review intended to summarize the role that oxidative stress and GSH play. Design • The research team performed a literature review from 1980 to the present that was based on the following keywords: oxidative stress, oxidation, antioxidant, and GSH in common ENT conditions. The review found the following conditions: (1) rhinitis, (2) allergic rhinitis, (3) chronic rhinosinusitis (CRS), (4) CRS with polyps, (5) otitis media with effusion, (6) chronic otitis media (COM), (7) COM and cholesteatoma, (8) tympanic membrane sclerosis, (9) tonsillitis, (10) Meniere's disease, (11) laryngeal conditions, and (12) chronic cough. Results • ENT conditions have been found to be associated with oxidative stress and with low GSH. A limited number of the reviewed studies discussed antioxidant use or repletion of GSH. Although only a few reports support the use of GSH or antioxidants as adjuncts in the management of ENT conditions, no reports of side effects were found related to their use. Conclusions • Many ENT conditions are associated with oxidative stress and decreased GSH, both locally in the affected tissues and systemically. The oxidative stress of those conditions may be related to depletion of GSH, which is increased by the higher levels of O2 in the upper respiratory tract. A small number of studies have reported clinical benefits from the use of an antioxidant or GSH support. The findings of benefits and the lack of reports of side effects suggest that the clinical use of antioxidants and support with GSH in ENT conditions may be considered as adjuncts to conventional management and that more research is warranted.