Adolescents are disproportionately affected in humanitarian and fragile settings, where they will often find themselves in high-risk situations and may be forced to take on adult roles within their families and communities. They are also more likely to have poor well-being outcomes related to disrupted or no access to optimum nutrition, health services and protection, as well as opportunities for education, training, and employment. Our paper aims to provide an overview of current interventions focusing on adolescent well-being and to provide a set of policy and programmatic recommendations to prevent long-term consequences of crisis and conflict on adolescents’ lives. According to the UN H6+ Technical Working Group on Adolescent Health and Well-beings’ framework for adolescent well-being, this article analyses adolescents’ backgrounds and interventions oriented to them within humanitarian and fragile settings. In this sense, we refer to five domains that include: good health and optimum nutrition; connectedness, positive values and contribution to society; safety and a supportive environment; learning, competence, education, skills and employability; and agency and resilience.