Advances in biotechnology in the twenty-first century, fueled in large part by the field of synthetic biology, have greatly accelerated capabilities to manipulate and re-program bacteria, viruses, and other organisms. These genetic engineering capabilities are driving innovation and progress in drug manufacturing, bioremediation, and tissue engineering, as well as biosecurity preparedness. However, biotechnology is largely dual use, holding the potential of misuse for deliberate harm along with positive applications; defenses against those threats need to be anticipated and prepared. This chapter describes the challenges of managing dual-use capabilities enabled by modern biotechnology and synthetic biology and highlights a framework tool developed by a National Academies committee to aid analysis of the security effects of new scientific discoveries and prioritization of concerns. The positive aspects of synthetic biology in preparedness are also detailed, and policy directions are highlighted for taking advantage of the positive aspects of these emerging technologies while minimizing risks.