Depression is one of the most prevalent of the psychiatric disorders and is common among individuals with epilepsy. Depression often begins in adolescence. The present review focuses on adolescent depression. In particular, this review first summarizes the definition, description, and classification of adolescent depression. Next, potential causes of adolescent depression are reviewed from a vulnerability-stress perspective. This part of the review focuses on the role of stressors and how stressors interact with genetic, biological, cognitive, personality, and interpersonal vulnerabilities to predict adolescent depression. Last, clinical aspects of adolescent depression are reviewed, including treatment and prevention of depression and the relation to epileptic disorders in adolescence. In sum, a substantial percentage of youth with epilepsy and seizures exhibit depression, and many are not diagnosed or treated in a timely manner. The present review shows that there are valid, empirically based assessments, treatments, and preventions for depression in adolescence that hold promise for reducing the significant burden associated with depression.