Serotonin reuptake inhibitor medications and cognitive-behavioral therapy (CBT) are both effective treatments for pediatric obsessive-compulsive disorder (OCD). Despite recommendations that youth with OCD be treated with CBT alone or together with serotonin reuptake inhibitor medication, many youth are treated with medication alone or with non-CBT psychotherapy initially. Although effective, symptom remission with medication alone is rare (e.g., only 21.4% of youth achieved remission with sertraline in the Pediatric OCD Treatment Study, 2004) and residual symptoms often remain (e.g., 58% of subjects in the March et al. [1998] sertraline trial were not considered treatment responders). This paper reviews the literature on the efficacy of CBT for pediatric OCD, particularly as it relates to the treatment of youth with prior inadequate response to medication. It also describes an intensive, family-based CBT program for children and adolescents with OCD and support for its efficacy among those with prior partial- or nonresponse to medication. Finally, we present a case study of an adolescent girl with OCD who participated in the intensive treatment program after having limited benefit from medication and non-CBT psychotherapy and experienced a favorable response.