The discovery of nitric oxide in the 1980s unraveled the novel concept then that an endogenous production of a gaseous substance such as nitric oxide can impart critical physiologic functions in a variety of biological and pathological processes. Interestingly though, we have known for a longer period of time that there exists another gaseous molecule, carbon monoxide (CO), that can be generated endogenously. The heme oxygenase enzyme system generates the majority, if not, all of the endogenous CO. Accumulating data in recent years have lent an intriguing supposition that we need to regard CO beyond the old paradigm that it imparts only toxicity and lethality to organisms. Instead, we need to consider CO, at low physiologic concentration, to play critical physiologic roles in various pathophysiologic states. This forum will review this double-edge sword of CO.