A range of factors, including early experience, parent-child interaction patterns, biological factors, and life events, have been associated with the development of depression among adolescents. Relations between early experience, attachment insecurity, and later depression may be mediated by failures to develop adaptive social skills, the acquisition of maladaptive beliefs or schema, or neurochemical factors (such as altered hypothalamic-pituitary-adrenal response to stress, and changes in serotonergic, noradrenergic, and dopaminergic systems). Prevention and treatment models that attend to the full range of developmental, cognitive, social, and biological factors associated with risk for depression are needed. Such models must account for observed increases in rates of depression during adolescence, as well as for gender differences in rates of depression that become apparent at that time. The Treatment for Adolescents With Depression Study (TADS) treatment protocol attempts to systematically address cognitive, behavioral, and social factors associated with vulnerability for depression among youth. It is a developmentally sensitive, formulation-based treatment model.