ABSTRACT Current concerns about antidepressant efficacy in children and adolescents are reminiscent of the history of adult studies. Such awareness should temper these concerns, especially in view of the enormous progress in the last two decades of studies of adult depression. A number of methodologie, nosologie, developmental, and validity considerations may have hampered the child and adolescent studies to date; thus, with more careful consideration of past problem areas, future studies may yield more promising results. The next generation of treatment research in child and adolescent depression may require innovative, multisite, longitudinal treatment designs which allow the simultaneous possibility for the continuing clarification and validation of depressive syndromes and treatment-responsive subgroups.