The current special issue brings together intriguing and important cross-country comparisons of issues pertinent to early adolescence that can inform the design and implementation of broader and relevant public health prevention strategies. The findings illustrate the importance of cross-country analyses for better understanding a range of health-related factors, including risk behaviors, mental health concerns, life satisfaction, and parent-child communication and relationships. The findings also underscore the convergence across countries and cultures of risk and protective factors as well as their associations with adverse health outcomes. Taken as a whole, the findings demonstrate that there are different unmet needs among girls and boys. As such, the findings stress the importance of providing youth with targeted prevention approaches and also, where feasible, sex-specific prevention and intervention strategies to direct scarce resources where they are most urgently needed.