The US Department of Homeland Security, and other state and federal agencies, continues to express concern over the potential use of radioactive isotopes as a weapon of terror. Few emergency medicine and critical care physicians are familiar with the care and treatment of an accidentally or intentionally irradiated patient who is contaminated externally or internally. This article reviews basic radiobiology and the variety of clinical signs and symptoms exhibited by victims exposed to radiation. Preparation for patient receipt and emergency care, followed by definitive diagnosis using biodosimentry is also presented. Therapeutic measures continue to evolve for externally and internally exposed victims, including those with combined injuries caused by burns and trauma.