This article highlights the prevalence of co-occurring disorders among adolescents and underscores the complexity and opportunities of treating these patients in a systematic, comprehensive approach. As evidenced by this review, the need exists to develop and test models of care that integrate co-occurring disorders into both psychiatric and substance abuse treatment settings. The challenge for pediatric practitioners is to provide detailed assessments linked to evidence-based treatment plans to account for the variations in adolescent development and the unique risk factor profile of each patient. The issues related to co-morbidity are vast and continue to grow with rapidly increasing research literature.