Biodefense is an important part of the national defense strategy. Since the 9/11 terrorist attack and the anthrax mail incident, the US has attached great importance to the construction and deployment of the biodefense system, with the aim of preventing negative impacts of biological weapon attacks and biotechnology abuse on the US. The US biodefense plan is the national security and public safety plan based on risk prevention and a brand new strategic plan based on the development of bioscience and biotechnology. In view of this, administrations of Bush, Obama and Trump have vigorously implemented the biodefense plan by enacting a large number of legal documents and making financial appropriations, thus providing legal, financial and technical support for the development of the plan. Moreover, with the participation of federal government departments, state and local governments, biotechnology companies and universities, the establishment of federal agencies for antiterrorism activities, as well as the improvement of information system for bioterrorism management, a relatively complete biological defense system and security network are gradually being built. After years of development and reform, American biodefense plan has achieved more significant results and improved its ability to defend against biological threats, but some problems still exist. Valuable reference and lessons could be drawn from the development of American biodefense plan and the construction of the biodefense system.