This article reviews and comments on the recent Treatment for Adolescents With Depression Study (TADS) that found that cognitive behavior therapy (CBT) was less efficacious than fluoxetine alone and no more efficacious than pill placebo in the treatment of depression in adolescents. Adding CBT to fluoxetine, however, improved treatment response in terms of both the reduction of depressive symptoms and the prevention of harm-related adverse events, including suicide risk. The TADS project was impressive in many respects and generally conducted well. However, the version of CBT used in this study was a novel amalgamation of different approaches, and may have tried to do too much in an overly structured fashion, thereby possibly tying the hands of the more experienced therapists in the trial. We question, therefore, the adequacy with which CBT was implemented and the representativeness of the findings. To explore these issues, we recommend that (a) the results be broken down by therapist and site, and (b) the CBT as implemented in TADS be compared to that provided in other studies that have found greater change in adolescent depression. Finally, we also question whether it was premature to move to large multisite effectiveness trials before establishing the relative efficacy of the respective interventions.