The Health Behaviour in School-aged Children (HBSC) study is a large cross-national research study, conducted in partnership with the World Health Organization (WHO). The study has surveyed young people aged 11, 13 and 15 years every 4 years since the mid-1980s and has grown to include 50 countries across Europe, North America, and Western-Central Asia. Over the past 40 years more than 1.6 million students have participated. HBSC aims to advance understanding of adolescent health behaviours, health and wellbeing within social contexts, inform national and international health promotion policies and practice, and foster collaboration among researchers, policymakers, and practitioners. In this paper we share the history and development of the HBSC study covering: i) theory-driven and novel research impact, ii) unique long-term trends in adolescent health behaviours and perceived health and wellbeing, iii) methodological rigor to allow cross-national comparison, and iv) embedding youth involvement and maximizing policy impact.