The discovery of nitric oxide (NO) initiated a novel research field, gaseous signal molecules. Other two gaseous signal molecules, carbon monoxide (CO) and hydrogen sulfide (H2S), have been approved subsequently. All of these three gaseous signal molecules are generated endogenously and exert extensive biological effects. This article reviews the significance of gaseous signal molecules in the pathogenesis of cardiovascular diseases. In the cardiovascular system, the endogenous NO, CO and H2S form three specific and relevant pathways with their corresponding enzymes including nitric oxide synthase (NOS), heme oxygenase (HO), and cystathionine-gamma-lyase (CSE). The gaseous signal molecules not only participate in the maintenance of physiological function and structure of the cardiovascular system, but also exert important pathophysiological effects in the pathogenesis of cardiovascular diseases, such as hypertension, pulmonary hypertension, septic shock and atherosclerosis. Further studies on gaseous signal molecules will remarkably promote the basic research in the cardiovascular fields, and provide a novel direction for the clinical research as well.