Major depressive disorder in adolescents is associated with severe consequences including suicide. Early intervention is crucial for preventing such outcomes. Parents may be reluctant to pursue antidepressant therapy for their children because of concerns about 1) a potential risk of increased suicidal ideation and 2) the effect of these medications on brain development. This article discusses the current data about potential risks associated with antidepressant use in children and adolescents versus the risk of untreated illness on their development. It also reviews recent research that suggests combination treatment involving antidepressant medications such as fluoxetine and cognitive behavioral therapy may be particularly helpful to patients who show poor response to only one of these treatments.