Pediatric health care and research focus mostly on single morbidities, although the single-disease framework has been challenged. The main objective was to estimate associations between childhood mental disorders and physical diseases.; This study is based on weighted data (n = 6482) from the National Comorbidity Survey Replication Adolescent Supplement (age, 13-18 years). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition lifetime mental disorders were assessed using the fully structured World Health Organization Composite International Diagnostic Interview, complemented by parent report. Lifetime medical conditions and doctor-diagnosed diseases were assessed by adolescent self-report.; Of 6469 participants, 2137 (35.33%) reported at least one mental disorder and one physical disease. The most substantial associations included those between affective disorders and diseases of the digestive system (odds ratio [OR] = 3.46, 95% confidence interval [CI] = 2.28-5.24), anxiety disorders and arthritis (OR = 2.27, CI = 1.34-3.85), anxiety disorders and heart diseases (OR = 2.41, CI = 1.56-3.73), anxiety disorders and diseases of the digestive system (OR = 2.18, CI = 1.35-3.53), and eating disorders and epilepsy/seizures (OR = 5.45, CI = 1.57-18.87). Sociodemographic factors did not account for the association between mental disorders and physical diseases.; Findings suggest that mental disorders and physical diseases often co-occur in childhood. This association is a major public health challenge, and the child health system needs additional strategies in patient-centered care, research, medical education, health policy, and economics to develop well-coordinated interdisciplinary approaches linking mental and physical care in children.