Exposure to carbon monoxide (CO) during general anesthesia can result from volatile anesthetic degradation by carbon dioxide absorbents as well as re-breathing of endogenously produced CO. Although adherence to the Anesthesia Patient Safety Foundation guidelines reduces the risk of CO poisoning, patients may still experience a sub-toxic CO exposure during low-flow anesthesia. The consequences of such exposures are relatively unknown. In contrast to the widely recognized toxicity of high CO concentrations, the biological activity of low concentration CO has recently been shown be cytoprotective. As such, low dose CO is being explored as a novel treatment for a variety of different diseases. Here we review the concept of anesthesia-related CO exposure, identify the sources of production, detail the mechanisms of overt CO toxicity, highlight the cellular effects of low dose CO, and discuss the potential therapeutic role for CO as a part of routine anesthetic management.