CO is an insidious poison with many sources of exposure. CO poisoning produces diverse signs and symptoms, which often are subtle and can be misdiagnosed easily. Failure to diagnose CO poisoning may result insignificant morbidity and mortality and allow continued exposure to a dangerous environment. In the ED, a high index of suspicion must be maintained for occult CO exposure. Headache, particularly when associated with certain environments, and flulike illness in the wintertime with symptomatic cohabitants should raise the index of suspicion in the ED significantly for occult CO poisoning. Emergency treatment of CO poisoning begins with inhalation of supplemental oxygen and aggressive supportive care. HBOT accelerates dissociation of CO from hemoglobin and may prevent DNS. Absolute indications for HBOT for CO poisoning remain controversial, although most would agree that HBOT is indicated in patients who are comatose, are neurologically abnormal, have a history of loss of consciousness with their exposure, or have cardiac dysfunction. Pregnancy with an elevated CO-Hgb level (>15-20%) also is widely considered an indication for treatment. HBOT may be considered in patients who have persistent symptoms despite NBO, metabolic acidosis, abnormalities on neuropsychometric testing, or significantly elevated levels. The ideal regimen of oxygen therapy has yet to be determined, and significant controversy exists regarding HBOT protocols. The emergency physician may be confronted with the difficult decision regarding disposition and even transfer to a hyperbaric facility. Often the local medical toxicologist, poison control center, or hyperbaric unit can assist the emergency physician with the decision-making process.