Major Depressive Disorder (MDD) is experienced by a significant proportion of youth today, occurring at an earlier age than found in previous generations. Major Depressive Disorder can produce long-lasting detrimental effects on a child's life, which raises the question of etiology. Three areas were examined for evidence identifying specific determinants of Major Depressive Disorder in youth: biological factors, including studies on inherited characteristics; psychological factors, focusing on cognitive and affective activity; and environmental factors, such as stressful life events. The implications of the findings were then explored.