Evidence-based substance use prevention programs have proliferated in schools and are being adopted by districts in rural settings and internationally. Little attention, however, has been paid to the adaptation process that occurs when these programs are moved to different contexts. In this commentary, the authors draw upon their experience with program adaptation to identify 6 areas for consideration when school-based programs are introduced in rural areas and in other countries. A key conclusion that emerges is that evidence-based programs should not be changed randomly but should be modified based on a careful review of program content, the theoretical underpinnings involved, and the context of the new environment.