Many children and adults with Obsessive-Compulsive Disorder experience incomplete symptom relief despite treatment with several evidence-based interventions for OCD. Converging lines of evidence from genetic, neuroimaging, biochemical and pharmacological studies implicate the importance of abnormalities in the glutamate symptoms in the pathogenesis of OCD. Strong evidence suggests that oxidative stress may be important in the progression of several psychiatric disorders, especially psychotic and affective disorders. N-acetylcysteine (NAC) is a cheap, relatively safe over-the-counter supplement that crosses the blood-brain barrier and acts potentially as a glutamate modulating agent and antioxidant. NAC has demonstrated efficacy in the treatment of a wide variety of psychiatric conditions in individual randomized, controlled trials including psychosis, autism, bipolar depression, trichotillomania. A recent double-blind placebo-controlled in adults with SRI-refractory OCD demonstrated the efficacy of NAC compared to placebo. In this review we summarize the preclinical and clinical data demonstrating NAC is a potentially promising new pharmacological agent in the treatment of OCD.