Cyanide poisoning may result from different exposures: residential fires, industrial accidents, drug and plant intoxication. Clinical features include coma, respiratory arrest and cardiovascular collapse. The biological hallmark is lactic acidosis. A plasma lactate concentration > or = 10 mmol/L in fire victims without severe burns and > or = 8 mmol/L in pure cyanide poisoned patients is a sensitive and specific indicator of cyanide intoxication. Many antidotes are available and efficient. However, therapeutic strategies are still debated. Our objective was to compare conventional treatments to hydroxocobalamin. This article reviews the literature on cyanide poisoning treatment. Conventional treatment of cyanide poisoning includes decontamination, supportive and specific treatment. Decontamination should be adapted to the route of poisoning and never postpone supportive treatment. Basic life support includes immediate administration of high flow of oxygen, airway protection and cardiopulmonary resuscitation. Advanced life support includes mechanical ventilation, catecholamine and sodium bicarbonate infusion. Supportive treatment is efficient but does not modify the time course or the body burden of cyanide. Numerous antidotes are available. Oxygen counteracts efficiently cyanide action at the mitochondrial level. Sodium thiosulfate, methemoglobin forming agents and cobalt compounds act efficiently by complexing or transforming cyanide into non-toxic stable derivatives. However, regarding the main clinical condition of cyanide poisoning, i.e. smoke inhalation, we should take into account not only the efficiency of antidotes but also their safety. Sodium thiosulfate is both efficient and safe, but acts with delay. Methemoglobin-forming agents are potent, but due to the transformation of hemoglobin into methemoglobin, they impair tissue delivery of oxygen. Experimental data showed increased mortality in carbon monoxide- and cyanide-poisoned rats treated with these agents. Cobalt EDTA and hydroxocobalamin are efficient and act immediately. Cobalt EDTA is more potent on a molar basis; however, numerous side effects limit its use to evidenced cyanide poisoning. In a prospective study, hydroxocobalamin appeared safe in fire victims with or without cyanide poisoning. The only reported side effect was a red coloration of skin and urine. In conclusion, antidotes are beneficial in cyanide poisoning. In suspected cyanide-poisoned patients, we recommend the use of hydroxocobalamin as first-line antidote, owing to its safety. In massive cyanide poisoning, due to the limited potency of hydroxocobalamin, continuous infusion of sodium thiosulfate should be associated.