During the degradation of heme by the enzyme heme oxygenase (HO), Carbon monoxide (CO) is generated. Although it is considered as a non-significant and potentially toxic waste gas of heme catabolism, CO is a key signaling molecule used to regulate different cardiovascular functions. In this review, we focus the protective roles of CO in vascular injury/disease, which may be important to explore the overall protective roles of HO-1/CO system in the pathogenesis of human vascular disease.