TADS randomly assigned 439 adolescents with MDD to 1 of 4 treatments: fluoxetine alone (FLX), cognitive-behavioral therapy alone (CBT), a combination of FLX and CBT (COMB), and a pill placebo (PBO). Results show that even the most effective treatment (COMB) was not very effective for many of the youths treated. Sixty-five percent of COMB-treated patients remained substantially impaired by MDD at the end of 12 weeks of treatment. Given the TADS findings of less than optimal outcomes for many youths, coupled with the known adverse impact of adolescent MDD on adult outcomes, there is an urgent need to test various treatments and treatment combinations beyond those tested in the TADS. Unfortunately medications that target different receptors or therapies that address various psychosocial risk factors for MDD are few. New studies of existing treatments and treatment combinations and entirely new treatments require creative, committed, and well-trained researchers; however, in the current era, embarking on such careers is an increasingly uncertain professional choice. The National Institute of Mental Health, which funded the TADS, must base its funding decisions on open discussion about how much of the Federal research budget should go to long-term research on genes of uncertain effect and unclear therapeutic relevance for polygenic disorders. Such funding must be balanced against funding for the development of currently available therapeutic strategies for youth with MDD. The TADS has shown that treatments for adolescents with MDD are available that are better than doing nothing, but they are not enough for many youth with MDD. This requires that the search for new treatments continue. 23 references