Glutathione is an endogenous antioxidant and has a ubiquitous role in many of the body s defences. Treatment with N-acetylcysteine (NAC) has been shown to increase levels of glutathione. NAC has been proposed as a treatment for several illnesses. Objectives: The efficacy and tolerability of NAC was examined across a range of conditions to evaluate the evidence supporting the use of NAC for each indication. Methods: A literature search was conducted using PubMed. Information was also collected from other online sources including the websites of the Therapeutic Goods Administration of Australia and the FDA. Results: Reports ranged from case studies to clinical trials. There is strong evidence to support the use of NAC for the treatment of paracetamol overdose and emerging evidence suggesting it has utility in psychiatric disorders, particularly schizophrenia and bipolar disorder. NAC is safe and well tolerated when administered orally but has documented risks with intravenous administration.