Tremendous advances in understanding the structure and function of the superfamily of phospholipase A(2) (PLA(2)) enzymes has occurred in the twenty-first century. The superfamily includes 15 groups comprising four main types including the secreted sPLA(2), cytosolic cPLA(2), calcium-independent iPLA(2), and platelet activating factor (PAF) acetyl hydrolase/oxidized lipid lipoprotein associated (Lp) PLA(2). We review herein our current understanding of the structure and interaction with substrate phospholipids, which resides in membranes for a representative of each of these main types of PLA(2.) jlr We will also briefly review the development of inhibitors of these enzymes and their roles in lipid signaling.-Burke, J. E., and E. A. Dennis. Phospholipase A(2) structure/function, mechanism, and signaling. J. Lipid Res. 2009. S237-S242.