Once widely regarded as a rare psychodynamic illness, obsessive-compulsive disorder (OCD) is now recognized as a common neurobiological condition affecting 1 in 50 US citizens. The etiology of the illness is still not clearly understood, but the observed therapeutic response in OCD patients to the potent serotonin uptake inhibitor clomipramine hydrochloride (CMI), guided research in the direction of neuronal brain function, and abnormalities of postsynaptic serotonin receptors are currently the leading hypotheses in the pathophysiology of OCD. Clomipramine, an analog of the tricyclic antidepressant imipramine, was the first effective antiobsessional agent available in the US. Clomipramine was, for some time, the treatment of choice for OCD given its superiority over other TCAs which lack potent serotonergic effects. Attention has now shifted to the selective serotonin reuptake inhibitors (SSRIs) whose potent and highly selective serotonin uptake properties account for their antiobsessional efficacy and favorable side effect profiles. The benefits of fluvoxamine, fluoxetine and sertraline have been shown in a number of clinical trials. This paper reviews the epidemiology, etiology, diagnosis and pharmacologic treatment studies of OCD. It summarizes two studies evaluating the efficacy of the SSRI sertraline, which is shown to be effective and well tolerated for both short- and long-term treatment of OCD.