Obsessive-compulsive disorder (OCD) is a chronic, disabling anxiety disorder that is characterized by recurrent obsessions and uncontrolled compulsions such as repetitive behavioral or mental acts that are performed in response to an obsession. OCD often occurs comorbidly with a number of depressive and anxiety disorders. In addition, patients with OCD suffer significant personal and social morbidity and may have difficulty maintaining a job, finishing school, and developing relationships. The backbone of pharmacologic treatment for OCD is a 10- to 12-week trial with a selective serotonin reuptake inhibitor (SSRI) in adequate doses. In most cases, treatment should be initiated with an SSRI because of the superior safety, tolerability, and equivalent efficacy of this class of drugs compared with clomipramine. When dealing with patients who do not respond to one SSRI, effective alternatives include switching to a different SSRI, combining another medication or behavioral therapy with SSRI therapy, considering novel or experimental drug treatments, or employing nonpharmacologic biological approaches, such as electroconvulsive therapy, neurosurgery, or repetitive transcranial magnetic stimulation. This article provides an update on the diagnosis and medical management of OCD and will discuss guidelines for the use of SSRIs and novel approaches for managing treatment-refractory patients.