In 2016, UNICEF hosted The Adolescent Brain: A second window of opportunity, a symposium that brought together experts in adolescent neuroscience to discuss this emerging science and how we can apply it to support all adolescents – but especially those already facing risks to their well-being, including poverty, deprivation, conflict and crisis. The articles in this compendium elaborate on some of the ideas shared at the symposium. Together, they provide a broad view of the dynamic interactions among physical, sexual and brain development that take place during adolescence. They highlight some of the risks to optimal development – including toxic stress, which can interfere with the formation of brain connections, and other vulnerabilities unique to the onset of puberty and independence. They also point to the opportunities for developing interventions that can build on earlier investments in child development – consolidating gains and even offsetting the effects of deficits and traumas experienced earlier in childhood.