Sphingosine-1-phosphate (S1P) is an important sphingolipid molecule involved in regulating cardiovascular functions in physiological and pathological conditions by binding and activating the three G protein-coupled receptors (S1PR1, S1PR2, and S1PR3) expressed in endothelial and smooth muscle cells, as well as cardiomyocytes and fibroblasts. It exerts its actions through various downstream signaling pathways mediating cell proliferation, migration, differentiation, and apoptosis. S1P is essential for the development of the cardiovascular system, and abnormal S1P content in the circulation is involved in the pathogenesis of cardiovascular disorders. This article reviews the effects of S1P on cardiovascular function and signaling mechanisms in different cell types in the heart and blood vessels under diseased conditions. Finally, we look forward to more clinical findings with approved S1PR modulators and the development of S1P-based therapies for cardiovascular diseases.