Tobacco use is the leading cause of preventable death in the U.S. Most daily smokers (82%) began smoking before age 18, and more than 3,000 young persons begin smoking each day. School programs designed to prevent tobacco use could become one of the most effective strategies available to reduce U.S. tobacco use. The following guidelines summarize school-based strategies most likely to be effective in preventing tobacco use among youth. They were developed by CDC in collaboration with experts from 29 national, federal, and voluntary agencies and with other leading tobacco-use prevention authorities to help school personnel implement effective tobacco-use prevention programs. These guidelines are based on an in-depth review of research, theory, and current practice in school-based tobacco-use prevention. The guidelines recommend that all schools: a) develop and enforce a school policy on tobacco use, b) provide instruction about the short-term and long-term negative physiologic and social consequences of tobacco use, social influences on tobacco use, peer norms regarding tobacco use, and refusal skills, c) provide K-12 tobacco-use prevention education, d) provide program-specific training for teachers, e) involve parents or families in support of school-based programs to prevent tobacco use, f) support cessation efforts among students and all school staff who use tobacco, and g) assess the tobacco-use prevention program at regular intervals.