To discuss the past, present, and future directions of school-based tobacco use prevention and cessation research. Discuss the origins of tobacco use prevention research; how prevention research advanced with empirical etiologic work; the genesis of comprehensive social influences programming and its contents; multiple modalities of programming beyond the school setting; and the rebirth of teen cessation programming and the issue of dissemination. There are many avenues of teen tobacco use prevention and cessation research and practice that need continued exploration, particularly regarding effects mediation and teen cessation. This discussion provides a background to assist health behavior researchers and practitioners to move forward in this arena.