Pharmacotherapeutic options for obsessive-compulsive disorder (OCD) have expanded over the past half-century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first-line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment-refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device-based approaches for treatment-refractory OCD are reviewed.