The childhood years represent a critical time for tobacco experimentation and addiction. This chapter presents risk factors for youth smoking, state of the science of nurse-led primary and secondary tobacco prevention research in youth, and implications for future research, policy, and practice. Nursing research on both primary and secondary tobacco prevention efforts that are school-based, family-based, and community-based are presented. Interventions, including both state and community approaches, and media and policy endeavors to prevent tobacco use and foster successful cessation are discussed. The nursing profession has made an impact on primary and secondary prevention in youth regarding tobacco; however, much remains to be accomplished. As one of the largest health care professions, nurses should seize the important opportunity of positively impacting the health of children and youth through comprehensive and effective primary and secondary tobacco prevention efforts.