The Treatment for Adolescents With Depression Study (TADS) is an NIMH-supported multisite clinical trial that compares the effectiveness of a depression-specific cognitive behavioral therapy (CBT), medication management with fluoxetine (FLX), the combination of CBT and FLX (COMB), and medical management with pill placebo (PBO). TADS was specifically designed as a comprehensive effectiveness study, able to answer clinically meaningful questions by including a broad and representative sample of depressed teens, delivering treatment at both tertiary medical centers and community clinics, and assessing functional as well as symptomatic outcomes. This report supports the importance of conducting clinical trials in youth with depression to bridge the gap between science and practice.