The Treatment for Adolescents With Depression Study (TADS) derives substantial public health significance from its head-to-head comparisons of carefully administered medication versus a carefully crafted cognitive-behavioral therapy in youth with major depression, the first major clinical trial of its kind. Although the study has a number of limitations, to include somewhat higher than expected socioeconomic status of participants and a somewhat lower than expected rate of minority participation, it stands as an investigation of major international significance in our understanding of effective treatments for adolescents with major depressive disorder. Further studies will need to ensure that its findings are broadly generalizable across the U.S. population, and to parse out the active ingredients of psychotherapies and determine how those active ingredients are related to changes in psychological mechanisms related to depressive disorders.