The aim of this literature review is to summarize the existing knowledge regarding the pathophysiology, clinical presentation, diagnosis and treatment of the asphyxiants carbon monoxide and cyanide. These asphyxiants both impair cellular oxygen utility by inhibiting either the transport or the consumption of oxygen in the body. Still, their modes of action are not entirely understood and are surrounded by some controversy. This holds true especially for carbon monoxide. Their toxidromes share similarities with hypoxia of other reasons. There are however some clinical elements that diverge, although no pathognomonic signs or symptoms have been recognized. Diagnosis of intoxication relies heavily on the initial clinical suspicion in addition to laboratory tests. This follows as the available laboratory tests for cyanide are slow and the measurement of COHb to recognize carbon monoxide intoxication does not identify all the affected cases. The established treatment for carbon monoxide intoxication is primarily normobaric oxygen therapy and hyperbaric oxygen therapy. The latter is nevertheless subject of controversy. The treatment for cyanide intoxication is oxygen and supportive care, combined with specific cyanide antidotes.