This article provides an overview of several interactive, computer-based substance abuse-prevention and -treatment interventions that we have developed for adolescents, including an interactive substance abuse-prevention multimedia program for middle school-aged youth and a customizable program focused on prevention of HIV, hepatitis, and sexually transmitted infections among youth in substance abuse treatment. The content in these programs is grounded in a scientific understanding of the types of skills and information that are critical to effective prevention. The programs also use several evidence-based informational technologies that have been shown to be critical in effectively training key skills and information. Our evaluations to date have underscored the effectiveness of these programs in producing desired health-behavior change. Applying information technologies to the delivery of science-based interventions may allow for unique opportunities to provide widespread dissemination of cost-effective interventions with consistency and in a manner that is engaging and acceptable to youth.