The deadliest form of a biological attack is aerosolized agents dispersed into the atmosphere. Early detection of aerosolized biological agents is important for defense against these agents. Because of the wide range of possible attack scenarios and attack responses, there is also a wide range of detector requirements. This article focuses on real-time, single-particle, optically based bio-agent trigger detectors--the first responder to an aerosol attack--and how to engineer these detectors to achieve optimal detection performance.