As biological research and its applications rapidly evolve, new attempts at the governance of biology are emerging, challenging traditional assumptions about how science works and who is responsible for governing. However, these governance approaches often are not evaluated, analyzed, or compared. This hinders the building of a cumulative base of experience and opportunities for learning. Consider “biosecurity governance,” a term with no internationally agreed definition, here defined as the processes that influence behavior to prevent or deter misuse of biological science and technology. Changes in technical, social, and political environments, coupled with the emergence of natural diseases such as coronavirus disease 2019 (COVID-19), are testing existing governance processes. This has led some communities to look beyond existing biosecurity models, policies, and procedures. But without systematic analysis and learning across them, it is hard to know what works. We suggest that activities focused on rethinking biosecurity governance present opportunities to “experiment” with new sets of assumptions about the relationship among biology, security, and society, leading to the development, assessment, and iteration of governance hypotheses.