Evaluations of public programs in many fields reveal that different types of programs—or different versions of the same program—vary in their effectiveness. Moreover, a program that is effective for one group of people might not be effective for other groups, and a program that is effective in one set of circumstances may not be effective in other circumstances. This paper presents a conceptual framework for research on such variation in program effects and the sources of this variation. The framework is intended to help researchers—both those who focus mainly on studying program implementation and those who focus mainly on estimating program effects—see how their respective pieces fit together in a way that helps to identify factors that explain variation in program effects, and thereby support more systematic data collection. The ultimate goal of the framework is to enable researchers to offer better guidance to policymakers and program operators on the conditions and practices that are associated with larger and more positive effects.