Inhalation injury is most commonly associated with damage to the mucosal surfaces of the small and large airways after exposure to smoke and other products of incomplete combustion. Yet, there are far deadlier things lurking within the smoke than just the heat and particulate matter: carbon monoxide and cyanide. These two toxic substances are found in varying concentrations within the fire room and are associated with early on-scene death and in-hospital morbidity and mortality. Patients suffering from carbon monoxide and/or cyanide poisoning present with vague symptoms requiring an astute physician to make the diagnosis. Fortunately, the toxic effects related to exposure to these agents can be reversed with readily available antidotes.