Obsessive-compulsive disorder (OCD) is a disabling psychiatric condition affecting 1-2% of the community. Although modern drug, behavioral and psychosurgical therapies have improved the prognosis of OCD considerably, approximately 30% of patients remain treatment-refractory. Currently, selective serotonin (5-HT) reuptake inhibitors (SSRIs) are the drug treatments of choice for OCD. Accordingly, this review evaluates the evidence for a role of the serotonin (5-HT) neurochemical system in the treatment and pathophysiology of OCD. However, drug treatment approaches that modify function of interrelated neurochemical systems, such as the dopamine and glutamate systems, are also briefly discussed as they promise to complement and enhance SSRI treatment effects.