The pathogenicity, transmissibility, environmental stability, and potential for genetic manipulation make microbes hybrid threats that could blur the distinction between peace and war. These agents can fall below the detection, attribution, and response capabilities of a nation and seriously affect their health, trade, and security. A framework that could enhance horizon scanning regarding the potential risk of microbes used as hybrid threats requires not only accurately discriminating known and unknown pathogens but building novel scenarios to deploy mitigation strategies. This demands the transition of analyst-based biosurveillance tracking a narrow set of pathogens toward an autonomous biosurveillance enterprise capable of processing vast data streams beyond human cognitive capabilities. Autonomous surveillance systems must gather, integrate, analyze, and visualize billions of data points from different and unrelated sources. Machine learning and artificial intelligence algorithms can contextualize capability information for different stakeholders at different levels of resolution: strategic and tactical. This document provides a discussion of the use of microorganisms as hybrid threats and considerations to quantitatively estimate their risk to ensure societal awareness, preparedness, mitigation, and resilience.