Carbon monoxide is generally believed to be a 'toxic' gas molecule due to its binding capability with hemoglobin. Overexposure to carbon monoxide leads to a hypoxic state that may cause the death of a mammalian. In contrast, directly exposure of carbon monoxide may protect cells or organs from various disease insults. The paradox effects of carbon monoxide might vary on the ways of exposure and the amounts being exposed. Here we highlighted the characteristics of this gas molecule and summarized its protective effects and therapeutic potentials in liver diseases and liver transplantation.