Science-based, preventive regulation was slow in coming to food law. It took more than half a century from the development of Hazard Analysis and Critical Control Point (HACCP) in the 1950s for Congress to direct the Food and Drug Administration (FDA) to apply comprehensive, science-based, preventive controls across the food supply. Full implementation will likely take several years, but the FDA Food Safety Modernization Act (FSMA) signed into law on January 4, 2011, provides FDA with a mandate to shift the focus of the FDA from primarily reacting to food safety problems to prevention. This chapter summarizes the evolution of science-based risk control systems into food regulation in the United States beginning with the development of HACCP and finishing with enactment of the Food Safety Modernization Act. Key points of the HACCP regulation for seafood, meats and poultry, juices, and FSMA risk control plans are covered. Finally, the chapter provides advice on compliance with these control systems.