Heme oxygenase (HO) catabolizes heme into three products: carbon monoxide (CO), biliverdin and free iron. HO-1, inducible form of HO, has been shown to be protective against various stress. CO at a low concentration has been shown to be protective in several disease models mimicking the action of HO-1. We suggest that CO, the byproduct of heme degradation, could be valuable therapeutic agents. We review the functional role of HO-1 and CO and its potential application to clinical settings.