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The topic of weapons of mass destruction (WMD) and related injuries is vast. The following article provides highlights of WMD and references the importance of personal protective equipment and decontamination. In your role as a pre-hospital care provider, it is unlikely that you will know the exact agent you will need to manage. It is important to recognize patterns of symptomatology to first, protect yourself and second stabilize your patients. Weapons of mass destruction can be summarized by the acronym CBRNE, which stands for Chemical, Biological, Radiological, Nuclear, and Explosive. We will highlight key features in each of the categories. In responding to a WMD incident, the responder must consider not only the agent in question, but also the route of dispersal as this can modify operations including personal protective equipment (PPE), a method of decontamination, and expectation to the number of possible victims. Route of dispersal can be through aerosolization, thermal detonation, contamination of water and food supply, and even human-to-human contact. The ideal model of transmission is dependent on the individual properties of each agent.