This paper describes efforts that began in the 1970s to prevent alcohol and drug abuse among adolescents in Chile and discusses current health promotion programs that focus on prevention of health-endangering behaviors. Adolescent substance abuse has been found to be strongly correlated with familial dysfunction and parental drug abuse as well as with certain behavioral characteristics. Therefore, prevention activities should target high-risk children as identified by screening instruments. Interventions should be carried out at the individual, school, family, community, and societal levels. It is important to analyze the feasibility of implementing prevention activities and to systematically evaluate their effectiveness.