Carbon monoxide (CO) poisoning continues to be a significant health problem both in the United States and in many other countries. CO poisoning is associated with a high incidence of severe morbidity and mortality. Epidemics of CO poisoning commonly occur during winter months and sources include: smoke from fires, fumes from heating systems burning fuels, and exhaust fumes from motor vehicles. The history of exposure and carboxyhemoglobin levels should alert the physician to this diagnosis. In the absence of exposure history, CO poisoning should be considered when two or more patients are simultaneously sick. The clinical presentation is non-specific and may range from nausea and headache to profound central nervous system dysfunction. The mainstay of therapy for CO poisoning is supplemental oxygen, ventilatory support, and monitoring for cardiac dysrhythmias. This article reviews up-to-date information of this potentially devastating exposure.