Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.