The Johns Hopkins Center for Health Security is working to analyze and deepen scientific dialogue regarding potential global catastrophic biological risks (GCBRs), in a continuation of its mission to reduce the consequences of epidemics and disasters. Because GCBRs constitute an emerging policy concern and area of practice, we have developed a framework to guide our work. We invited experts from a variety of disciplines to engage with our underlying concepts and assumptions to refine collective thinking on GCBRs and thus advance protections against them.