Abstract Depression in adolescence and adulthood is common, afflicting up to 20 percent of these populations. It represents a significant public health concern and is associated with considerable suffering and functional impairment. Adolescent-onset depression tends to be a particularly malignant and recalcitrant condition, increasing the likelihood of recurrence and chronicity in adulthood. Clinical presentations for various medical and psychiatric conditions, as well as reactions to psychosocial stressors, can mimic or confound the picture of depression in adolescents. Therefore, careful assessment and differential diagnosis is essential. Effective treatments, both pharmacological and psychosocial in nature, exist, and so early detection and intervention is paramount. This article presents an overview of optimal prevention, assessment, and clinical decision-making strategies for managing depression in adolescents.