Phospholipase A(2) (PLA(2)) constitutes a growing superfamily of lipolytic enzymes, and to date, at least 19 distinct enzymes have been found in mammals. This class of enzymes has attracted considerable interest as a pharmacological target in view of its role in lipid signaling and its involvement in a variety of inflammatory conditions. PLA(2)s hydrolyze the sn-2 ester bond of cellular phospholipids, producing a free fatty acid and a lysophospholipid, both of which are lipid signaling molecules. The free fatty acid produced is frequently arachidonic acid (AA, 5,8,11,14-eicosatetraenoic acid), the precursor of the eicosanoid family of potent inflammatory mediators that includes prostaglandins, thromboxanes, leukotrienes and lipoxins. Multiple PLA(2) enzymes are active within and surrounding the cell and these enzymes have distinct, but interconnected roles in AA release.