Sulfur dioxide is considered a toxic gas in air pollution and detrimental to many organs, however, it can be generated endogenously in the cardiovascular system in vivo. Gaseous sulfur dioxide has an endothelium-dependent vasorelaxing effect at low concentrations, but is endothelium-independent at high concentrations and has a negative inotropic effect on cardiac function. This vasorelaxing effect is mediated by adenosine triphosphate-sensitive calcium channels and L-type calcium channels. Under pathophysiological conditions, sulfur dioxide increases anti-inflammatory response and antioxidant capacities in pulmonary hypertensive rats. Sulfur dioxide also attenuates increased blood pressure and vascular remodeling in spontaneously hypertensive and hypoxic pulmonary hypertensive rats. Recent studies suggest that endogenous sulfur dioxide is also involved in the process of myocardial ischemia-reperfusion injury and lipid metabolism. Therefore, the evidence suggests that endogenous sulfur dioxide may be a novel gasotransmitter in the cardiovascular system. The significance of sulfur dioxide on the cardiovascular system is intriguing and appealing.