In the past decade, prevention science has emerged as a discipline built on the integration of life course development research, community epidemiology, and preventive intervention trials [Am. Psychol. 48 (1993) 1013; Am. J. Community Psychol. 27 (1999) 463; Kellam, S. G., & Rebok, G. W. (1992). Building developmental and etiological theory through epidemiologically based preventive intervention trials. In J. McCord & R. E. Tremblay (Eds.), Preventing antisocial behavior: interventions from birth through adolescence (pp. 162–195). New York: Guilford Press.]. Prevention science is based on the premise that empirically verifiable precursors (risk and protective factors) predict the likelihood of undesired health outcomes including substance abuse and dependence. Prevention science postulates that negative health outcomes like alcohol abuse and dependence can be prevented by reducing or eliminating risk factors and enhancing protective factors in individuals and their environments during the course of development. A growing number of interventions have been found to be effective in preventing adolescent tobacco, alcohol, and other drug abuse, delinquency, violence, and related health risk behaviors by reducing risk and enhancing protection. During the same decade, comprehensive community-based interventions to prevent adolescent health and behavior problems have been widely implemented in the U.S. with federal and foundation support. Despite the advances in the science base for effective preventive interventions and the investments in community-wide preventive interventions, many communities continue to invest in prevention strategies with limited evidence of effectiveness [Am. J. Public Health 84 (1994) 1394; J. Res. Crime Delinq. 39 (2002) 3; J. Community Psychol. 28 (2000) 237; J. Community Psychol. 28 (2000) 237; J. Consult. Clin. Psychol. 67 (1999) 590; Eval. Program Plann. 20 (1997) 367.]. Translating prevention science into community prevention systems has emerged as a priority for prevention research [J. Community Psychol. 28 (2000) 363; J. Appl. Behav. Anal. 28 (1995) 479.]. The Communities That Care (CTC) prevention operating system is a field-tested strategy for activating communities to use prevention science to plan and implement community prevention systems. CTC provides tools that assist 122communities to use local data on risk and protective factors to identify elevated risks and depressed protective factors in geographic areas where levels of risk are high and levels of protection are low and then to implement tested, effective preventive interventions that reduce the identified risks and enhance protection in these [Developmental Research and Programs. (1997). Communities That Care: a comprehensive prevention program. Seattle, WA: Author; Developmental Research and Programs. (2000a). Communities That Care: a comprehensive prevention program. Seattle: Author; Hawkins, J. D., Catalano, R. F., Et al. (1992). Communities That Care: action for drug abuse prevention (1st ed.). A joint publication of the Jossey-Bass social and behavioral science series and the Jossey-Bass education series. San Francisco: Jossey-Bass]. The CTC system is widely implemented, and process evaluations of CTC suggest that it can assist communities to develop more effective prevention systems. This paper describes the background and use of the CTC operating system and results of evaluations of implementation of the system.