Obsessive-compulsive disorder (OCD) is a severe and debilitating illness. This chapter examines the available evidence regarding choosing a treatment modality, efficacy within modality classes, special groups, and augmentation strategies. It also reviews the latest advances in treatment. Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRI) monotherapy have each been shown in multiple randomized controlled trials to be efficacious for adults with OCD. Other than pharmacotherapy with a serotonin reuptake inhibitor, CBT is the only other first-line treatment for adults. New horizons for research include development of clinical correlates, or endophenotypes, of OCD symptoms in order to understand the underlying mechanism of disease. Translational approaches, such as developing mouse models of OCD and neuroimaging of the serotonin, dopamine, and glutamate neurotransmitter systems, will help us to understand better how neural substrates are linked to OCD and how our treatments affect these neural systems and reduce OCD symptoms.