The National Academies of Sciences, Engineering, and Medicine was asked to articulate a 5-year strategic vision for international health security programs and provide findings and recommendations on how to optimize the impact of the Department of Defense (DOD) Biological Threat Reduction Program (BTRP) in fulfilling its biosafety and biosecurity mission. Because BTRP is just one of several U.S. government programs conducting international health security engagement, both the strategic vision and the success of the program rely on coordinating actions with the U.S. government as a whole and with its international partners. This report provides several recommendations for optimizing BTRP success in its current mission and the wider-looking strategic vision it proposes.