The World Health Organization (WHO) is releasing the second edition of its Global Accelerated Action for the Health of Adolescents (AA-HA!) guidance. The document aims to equip governments to respond to the health and well-being challenges, opportunities and needs of adolescents. The guidance provides the latest available data on adolescent health and well-being. It also outlines an updated list of core indicators that data should be collected on. Globally, road injury was the top cause of death for adolescent males in 2019. Among female adolescents, the leading causes of death were diarrhoeal diseases among the younger group (10-14 years) and tuberculosis (TB) in the older group (15-19 years). Over the last 20 years, mortality rates have declined among adolescents globally, with the largest decline in older (15–19 years) adolescent girls. For non-fatal diseases, the burden has not improved over the past two decades, with the main causes of ill health in this category being: mental health conditions (depressive and anxiety disorders, childhood behavioural disorders), iron deficiency anaemia, skin diseases and migraine. Adolescent well-being depends on a range of factors, including healthy food, education, life skills and employability, connectedness, feeling valued by society, safe and supportive environments, resilience, and the freedom to make choices. To take an appropriately holistic approach, the guidance outlines how to take crosscutting action to support adolescent health and well-being, with mutually reinforcing interventions across sectors, such as health, education, social protection, and telecommunications. Targeted efforts are also required to engage adolescents, as they trust health systems less than adults do and are especially vulnerable to modern-day trends, like online bullying and gaming.