This article reviews recent research on the prevention of tobacco, alcohol, and drug abuse with children and adolescents. The review is organized according to an intervention focus on the agent, environment, and host. An original study describes methods and results of host-oriented skills intervention to prevent cigarette smoking. Based on the reviewed recent past studies, the authors note conceptual and methodological progress in substance abuse prevention research. Suggestions for future research include technological improvements necessary to implement preventive interventions on a wide scale. The authors highlight the importance of careful designs; manipulation checks on independent variables; process data collection; multimodal measures of self-report, behavioral, and physiological variables; and multivariate statistical analyses in studies on interventions to prevent tobacco, alcohol, and drug abuse with children and adolescents.