Introduction: Obsessive-compulsive disorder (OCD) is associated with significant morbidity and dysfunction. First-line OCD treatments - serotonin reuptake inhibitors (SRIs), cognitive behavioral therapy (CBT) and their combination - though widely used, are not sufficient in treating resistant cases. This eventually raises the need for finding novel strategies, whether by adding-on drugs or switching to a different psychopharmacological class. The aim of this paper is to present a comprehensive review of non-antidepressant pharmacological treatment that has been evaluated for the management of OCD. Materials and methods: A research has been conducted using MedLine and the following Medical Subject Headings (MeSH) terms were used: Obsessive compulsive disorder AND drug therapy. Articles that conformed to specific inclusion criteria were stratified per drug and per quality of evidence. For each drug, articles having the best level of evidence were retained. Results: Sixty-eight articles were reviewed and presented by drug class as follows: antipsychotics, mood stabilizers, gamma-amino-butyric acid (GABA) analogues and GABA reuptake inhibitors, benzodiazepines, glutamatergic agents and other miscellaneous drugs. Discussion: There is substantial collective evidence supporting the use of antipsychotics as an augmentation treatment of resistant OCD patients. Although not always consistent, the following drugs showed some efficacy upon randomized controlled trials: risperidone, olanzapine, quetiapine, aripiprazole, haloperidol, topiramate, pindolol, morphine, ondansetron and celecoxib. The efficacy of glutamatergic agents is promising. Numerous other pharmacological agents have been studied yet the results are inconclusive due to several limitations mainly of methodological nature.