Among the categories of Weapons of Mass Destruction (WMD)—chemical, biological, radiological, nuclear and explosive, the two that revive images of horror on a par with ‘doomsday’ scenarios are the radiological and nuclear agents. While all five pose a serious risk to health, and have been used by nations, terrorists and insurgents throughout human history, most healthcare professionals are familiar with treating trauma and have a background—at least rudimentary—in treating pathogens and certain chemical toxicants, although the WMD versions of pathogens and chemicals are clearly more dangerous. But few healthcare professionals have had the experience of working with, let alone recognizing or treating, a radiation‐induced illness or injury. In the December World at Risk Report published by the Commission on Weapons of Mass Destruction Proliferation and Terrorism impanelled by the US Government, their conclusion in terms of the availability of radiological and nuclear materials, entities willing to use them and the increased opportunity to develop weapons—rudimentary or otherwise was as follows: ‘The sobering reality is the risks are growing faster than our multilayered defences. Our margin of safety is shrinking, not growing’. Mass exposures to a radiological or nuclear event will pose a unique and unprecedented challenge—at least in the last 50 years—a challenge that health‐care professionals remain undertrained for, and most facilities continue to be untested and underprepared. Yet emergency medical services, hospitals and medical professionals are looked upon as the critical response arm of preparedness. While a nuclear or radiological event may be considered a low likelihood—it is clearly a high consequence exigency. As such, our facilities and healthcare professionals need to update or develop plans, increase training and implement more skills‐based efforts. The analogy is simple—our communities are depending upon us to save them… yet we do so with little more than perhaps annual drills or table‐top exercises. Would we allow a colleague to intubate one of our loved ones based upon practising that skill only once a year? Why then, facing the complexities of diagnosing and managing a radiation event in our region, would we be satisfied with single annual exercises? In the aftermath of the Litvinenko murder with polonium‐210, the increasing likelihood of Iran and other nations acquiring some form of radiological weaponry, re‐emergence of nuclear energy as an alternative to fossil fuels and the resulting proliferation of radioactive waste—now is the time to address radiation preparedness. Towards that end, this chapter will discuss the global threats, key medical considerations, essential equipment and other important issues necessary to enhance preparedness.