Carbon monoxide poisoning remains a leading cause of accidental poisoning worldwide (both at home and at work), and it is also a cause of suicidal poisoning. Such poisoning can arise following prolonged exposure to low levels of CO or following brief exposure to high concentrations of the gas. In fact, despite exposure limits, high safety standards, and the availability of CO alarms, nearly 50,000 people in the United States visit the emergency department each year due to poisoning. Additionally, CO poisoning in the United States causes up to 500 deaths each year. Despite the widespread nature of this form of poisoning, known about for centuries and whose damage mechanisms have been recognized (or rather hypothesized about) since the 1800s, early recognition, especially of late complications, and treatment remain a medical challenge. A well-designed therapeutic diagnostic process is necessary so that indication for hyperbaric or normobaric therapy is correctly made and so that patients are followed up even after acute exposure to diagnose late complications early. Furthermore, it is necessary to consider that in the setting of emergency medicine, CO poisoning can be part of a differential diagnosis along with other more frequent conditions, making its recognition difficult. The last thirty years have been marked by a significant increase in knowledge regarding the toxicity of CO, as well as its functioning and its importance at physiological concentrations in mammalian systems. This review, taking into account the significant progress made in recent years, aims to reconsider the pathogenicity of CO, which is not trivially just poisonous to tissues. A revision of the paradigm, especially as regards treatment and sequelae, appears necessary, and new studies should focus on this new point of view.