During the next decade we will see broad dissemination of a growing number of empirically validated school-based prevention programs. The processes of effectiveness research, broad program diffusion, and program integration at the school and community level will become a central focus of research activity. The paper presents six future directions for research in the field of school-based prevention and health promotion. The directions include developing new programs and models, developing standards and accountability systems related to school success, moving from efficacy to effectiveness research, understanding factors influencing program integration, broad dissemination of programs and policies, and the sustainability of programs, policies, and community partnerships. These future directions are driven by three significant research-to-service challenges faced both by practitioners and researchers that involve systems integration across developmental stages, levels of care, and institutional structures.