The increasing prevalence of co-occurring mental health and substance use disorders in adolescents is a serious challenge for the primary care system. The needs of these youth continue to be underrecognized, poorly diagnosed, and inappropriately treated in primary care settings, which are often the first point of contact with the health provider system. This article highlights the need for changes at the clinical, organizational, and policy levels to create a system of care that can effectively identify, refer, treat, and coordinate the care for these adolescents and their families.