Most of the randomized controlled trials (RCTs) on the acute treatment of children and adolescents with major depressive disorder (MDD) have shown about 50 percent response to both tricyclic antidepressants (TCAs) and placebo. In contrast, a recent RCT found fluoxetine superior to placebo for the treatment of depressed youth. Cognitive-behavioral psychotherapy has also been found efficacious for the treatment of youth with depression. Therefore, the use of medications in particular TCAs, as the first line of treatment for youth with mild to moderate MDD has been questioned. However, some subgroups of patients, especially those who are unable or unwilling to undergo psychotherapy and those with psychosis, bipolar depression, severe depressions, or recurrent episodes, may benefit from initial treatment with antidepressants. Further research on the continuation and maintenance treatment phases of depression as well as treatment for dysthymia, treatment-resistant depression, and other subtypes of depressions is warranted.