Why is adolescence an “age of risk” for onset of bipolar spectrum disorders? We discuss three clinical phenomena of bipolar disorder associated with adolescence (adolescent age of onset, gender differences, and specific symptom presentation) that provide the point of departure for this article. We present the cognitive vulnerability–transactional stress model of unipolar depression, evidence for this model, and its extension to bipolar spectrum disorders. Next, we review evidence that life events, cognitive vulnerability, the cognitive vulnerability–stress combination, and certain developmental experiences (poor parenting and maltreatment) featured in the cognitive vulnerability–stress model play a role in the onset and course of bipolar disorders. We then discuss how an application of the cognitive vulnerability–stress model can explain the adolescent age of onset, gender differences, and adolescent phenomenology of bipolar disorder. Finally, we further elaborate the cognitive vulnerability–stress model by embedding it in the contexts of normative adolescent cognitive (executive functioning) and brain development, normative adolescent development of the stress–emotion system, and genetic vulnerability. We suggest that increased brain maturation and accompanying increases in executive functioning along with augmented neural and behavioral stress–sensitivity during adolescence combine with the cognitive vulnerability–stress model to explain the high-risk period for onset of bipolar disorder, gender differences, and unique features of symptom presentation during adolescence.Preparation of this article was supported by National Institute of Mental Health Grants MH 52617 (to L.B.A.) and 52662 (to L.Y.A.).