Practice guidelines for the treatment of youth with mental health problems tend to endorse integrating psychopharmacologic treatment with psychosocial interventions, such as psychotherapy and parent skills training. However, poor access to pediatric mental health specialists and inadequate training of primary care physicians in psychosocial interventions make it difficult for families to receive this standard of care. Large pediatric randomized, multicenter trials, including the Multimodal Treatment Study of ADHD (attention deficit hyperactivity disorder) [MTA] and the Treatment for Adolescents with Depression Study (TADS), have begun to identify specific advantages of multimodal treatment compared with psychopharmacology alone. Advantages of combined treatment include improvement of both symptoms and family functioning. More research is needed to determine effective and appropriate multimodal interventions for complex and severe pediatric mental illness. Advantages of multimodal treatment must be balanced with the treatment burden on the family system.