A wide variety of prevention approaches that reduce substance use and associated problems have been developed and tested. But successes have been limited in promoting the use of these scientific advances by the policy makers, practitioners, and concerned citizens. The Center for Substance Abuse Prevention's six regional Centers for the Application of Prevention Technologies (CSAP's CAPTs) are a major mechanism by which CSAP brings research to practice. This article synthesizes the issues that the CAPTs have faced, the solutions they have developed, and conclusions concerning the work that still needs to be done to increase the application of science-based approaches to prevention. These discussions highlight the particular importance of addressing issues related to the larger systems in which prevention programs and strategies operate.