The International Programme on Chemical Safety (IPCS)-a cooperative program of the World Health Organization (WHO), the International Labour Organization (ILO), and the United Nations Environment Programme (UNEP)-designates cyanide a priority chemical in relation to the potential impact on human health and the environment. Like other IPCS priority chemicals, cyanide is highly toxic, is a transboundary safety concern, is a target for risk management in multiple countries, is produced in large quantities, has dispersive use, and poses a risk for human exposure (Table I).1 Acute exposure to cyanide has caused significant morbidity and mortality in household and industrial accidents, as well as in suicides and attempted genocides, wars, and acts of terrorism. The most common, but perhaps least recognized source of cyanide in cases of acute poisoning is from smoke caused by fires.2 This review is the product of a collaboration among experts in prehospital emergency medicine, public health and safety, and disaster preparedness. Current understanding of the causes, consequences, and management of cyanide poisoning are described as a potential advancement in antidotal therapy that could transform the provision of prehospital care to cyanide-poisoned victims.Cyanide originates either from natural or human-made sources and can exist in gaseous, liquid, and solid forms. 1 ' 3 It is among the most rapidly acting of poisons and, when present in sufficient concentrations, one of the most lethal. For example, exposure to moderate-to-high concentrations of hydrogen cyanide can result in death within seconds to minutes. Given the rapid progression of cyanide toxicity, prehospital responders arguably can impact the outcome of acute human exposure to cyanide more than any other category of healthcare provider. Prehospital responders usually are the first medical professionals to encounter and minister to the victim of cyanide poisoning. In many cases, whether the patient lives or dies depends largely on the prompt recognition of acute cyanide toxicity and/or interventions provided in the prehospital setting by the emergency responders.Standard supportive care, including administration of 100% oxygen and cardiopulmonary resuscitation can help counteract cyanide toxicity, but successful intervention for moderate-to-severe poisoning entails administration of an antidote in addition to these supportive measures. The US prehospital responder's role in administering antidotal treatment has been limited somewhat by the lack of out-of-hospital options that have a good risk:benefit ratio. The Cyanide Antidote Package (also known as the Cyanide Antidote Kit (CAK), the Lilly Kit, the Pasadena Kit, and the Taylor Kit) is the only antidote currently available in the United States. The CAK can be associated with toxicities including hypotension, which can exacerbate shock, and methemoglobinemia, which reduces the oxygen-carrying capacity of the blood and can be particularly dangerous in oxygen-deprived victims of smoke-inhalation. The potential...