Myocardial function is intimately dependent on the precise spatiotemporal regulation of membrane-bound proteins and ion channels. Phospholipases play critical roles in the maintenance of membrane structure and function, thereby fundamentally integrating dynamic alterations in myocardial performance with membrane composition and dynamics. The major phospholipases in myocardium belong to a family of proteins known as calcium-independent phospholipases (iPLA2s). In addition to their role in maintaining normal membrane structure and function, iPLA2 catalytic activity results in the generation of a variety of lipid second messengers that facilitate cellular signaling. Through its multiple effects on cardiac myocyte bioenergetics, cellular signaling, and membrane function, the iPLA2 family of enzymes is of primary importance in modulating the pathologic sequelae of myocardial ischemia, diabetic cardiomyopathy, and remodeling during hemodynamic stress. This review will provide a brief overview of myocardial iPLA2s and their significance in cardiac pathology and physiology.