Determining the best use of food safety resources is a difficult task faced by public policymakers, regulatory agencies, state and local food safety and health agencies, as well as private firms. The Food Safety Research Consortium (FSRC) has developed a conceptual framework for priority setting and resource allocation for food safety that takes full account of the food system’s complexity and available data but is simple enough to be workable and of practical value to decisionmakers. The conceptual framework addresses the question of how societal resources, both public and private, can be used most effectively to reduce the public health burden of foodborne illness by quantitatively ranking risks and considering the availability, effectiveness, and cost of interventions to address these risks. We identify two types of priority-setting decisions: Purpose 1 priority setting that guides risk-based allocation of food safety resources, primarily by government food safety agencies, across a wide range of opportunities to reduce the public health impact of foodborne illness; and Purpose 2 priority setting that guides the choice of risk management actions and strategies with respect to particular hazards and commodities. It is essential that such a framework be grounded in a systems approach, multi-disciplinary in approach and integration of data, practical, flexible, and dynamic by including ongoing evaluation and continuous updating of risk rankings and other elements. The conceptual framework is a synthesis of ideas and information generated in connection with and during the three FSRC workshops convened under a project funded by the Cooperative State Research, Education, and Extension Service of USDA. Workshop materials are available on the project website: http://www.card.iastate.edu/food_safety/.