Although numerous evidence-based programs (EBPs) have been proven effective in research trials and are being widely promoted through federal, state, and philanthropic dollars, few have been "scaled up" in a manner likely to have a measurable impact on today's critical social problems. The Interactive Systems Framework for Dissemination and Implementation (ISF) explicates three systems that are critical in addressing the barriers that prevent these programs from having their intended public health impact. In this article we describe the relevance of these systems in a real-world context with a specific focus on the Prevention Support System (PSS). We expand on the ISF model by presenting funders and policy-makers as active and engaged stakeholders, and demonstrate how a state-level PSS has used empirical evidence to inform general and program-specific capacity-building and support interactions among researchers, funders, and practitioners in Pennsylvania. By embracing this expanded ISF framework as a conceptual model for the wide-scale dissemination and support of EBPs, and recognizing the need for a distinct state-level PSS, Pennsylvania has created an infrastructure to effectively address the primary barriers to moving from lists of EBPs to achieving population-level public health improvement.