Phosphoinositides (PIs), a family of phosphorylated derivatives of the membrane lipid phosphatidylinositol, are established regulators of multiple cellular functions. An increasing amount of evidence has highlighted potential links between PI-mediated signaling pathways and the etiology of many human diseases, including cardiovascular pathologies. This chapter will provide a detailed overview of the peculiar functions of the major cardiovascular PIs in the pathogenesis of atherosclerosis, heart failure, and arrhythmias.