This article reviews use and depression in adolescents and explores the thesis that depressed mood and deviant actions represent deviant modes of coping and are the result of failed efforts to handle different and sometimes overlapping constitutional and social risk factors. Theories of drug use and depression and various studies in support of the theoretical framework are examined. Implications are suggested for public health interventions and clinical management as derived from the theoretic background and empiric evidence. Also provided are guidelines for assessment and intervention that can be useful for primary care physicians and other professionals working with troubled teenagers.