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The U.S. food supply chain is deeply interconnected with human and environmental health, as well as social and economic systems. To arrive at a decision whose benefits outweigh its risks, decision makers must carefully consider a broad range of effects and interactions across the health, environmental, social, and economic domains. To aid in this complex analytical process, the Institute of Medicine and the National Research Council convened an expert committee to develop a framework to assist in food and agriculture decision making. The committee’s report, A Framework for Assessing Effects of the Food System, sponsored by The JPB Foundation, presents guiding principles and practical steps to help stakeholders weigh tradeoffs and choose policies that integrate benefits and risks across various domains.