Licensed pharmacological treatments for obsessive-compulsive disorders include selective serotonin reuptake inhibitors and tricyclic antidepressants. However, a large proportion of patients show minimal or no therapeutic response to these treatments. The glutamatergic system has been implicated in the etiology of obsessive-compulsive spectrum disorders, and it has been postulated that n-acetyl-cysteine (NAC) could have a therapeutic effect on these conditions through its actions on the glutamatergic system and the reduction of oxidative stress. A systematic review was conducted on the existing methodologically robust literature regarding the efficacy of NAC on obsessive-compulsive spectrum disorders in adults and children. Four randomized, double-blind placebo-controlled studies were identified, investigating the effects of NAC on obsessive-compulsive disorder, trichotillomania, and onychophagia. Results remain inconclusive, but NAC may still be useful as a treatment for obsessive-compulsive spectrum disorders on an individual level, particularly as the compound has a relatively benign side-effect profile. The dearth of methodologically robust work is clinically important: larger randomized controlled trials are required to inform of any meaningful clinical effectiveness, and to better determine which, if any, clinical populations might most benefit.