The recent U.S. Congressional mandate for creating drug-free learning environments in elementary and secondary schools stipulates that education reform rely on accountability, parental and community involvement, local decision making, and use of evidence-based drug prevention programs. By necessity, this charge has been paralleled by increased interest in demonstrating that drug prevention programs net tangible benefits to society. One pressing concern is precisely how to integrate traditional scientific methods of program evaluation with economic measures of “cost efficiency”. The languages and methods of each respective discipline don’t necessarily converge on how to establish the true benefits of drug prevention. This article serves as a primer for conducting economic analyses of school-based drug prevention programs. The article provides the reader with a foundation in the relevant principles, methodologies, and benefits related to conducting economic analysis. Discussion revolves around how economists value the potential costs and benefits, both financial and personal, from implementing school-based drug prevention programs targeting youth. Application of heterogeneous costing methods coupled with widely divergent program evaluation findings influences the feasibility of these techniques and may hinder utilization of these practices. Determination of cost-efficiency should undoubtedly become one of several markers of program success and contribute to the ongoing debate over health policy.