Biosafety—keeping laboratory workers, the community, and the environment safe—is a crosscutting need for all research activities, as well as an important research and policy area with medical, political, and security consequences. As such, it requires a dedicated plan for the US government. One reason biosafety is attracting more attention now is because it may be a limiting factor in the development of advanced biotechnologies. Many potential new biotechnology applications with biomedical and economic implications are intended to be used outside the laboratory and released into the environment, so their safety cannot rely on traditional laboratory containment. They are meant to be “outside.” Applications such as mosquito control, agriculture, pollution remediation, mining, biofuels, medications that use synthetic organisms to treat gastrointestinal diseases, or even the re-creation of extinct animals require synthetic organisms to be in the environment, where they can interact with other living things. These applications may be tremendously beneficial and may spur economic development, but if biosafety risks are not addressed and carefully thought through, they could yield unintended and accidental consequences.