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Managing casualties in chemical, biological, radiological, and nuclear (CBRN) incidents poses distinct challenges. These events have a disproportionate impact on both emergency personnel and infrastructure. While encounters with CBRN incidents are rare, it’s essential to plan and train comprehensively, employing a universal approach to all potential hazards. Effectively managing CBRN incidents necessitates prompt identification of the agent involved, demanding specialized knowledge among responders. Understanding factors such as toxicity, latency, and persistency is critical in handling chemical incidents for appropriate casualty prioritization and intervention. Distinguishing between live biological agents and toxins is crucial in managing biological threats. The characteristics of live agents, including virulence, pathogenicity, infectivity, transmissibility and lethality, vary and require tailored management. Similarly, radiological and nuclear hazards, which may result in irradiation, contamination, or trauma, demand a structured approach to response efforts during major incidents. All healthcare professionals involved in such incidents must grasp the principles of CBRN incident management to mount a proficient reaction.