Phospholipase A 2 (PLA 2 ) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins and leukotrienes. The same reaction also produces lysophosholipids, which represent another class of lipid mediators. So far, at least 19 enzymes that possess PLA 2 activity have been identified and cloned in mammals. The secretory PLA 2 (sPLA 2 ) family, in which 10 isozymes have been identified, consists of low-molecular weight, Ca 2+ -requiring secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, and host defense. The cytosolic PLA 2 (cPLA 2 ) family consists of three enzymes, among which cPLA 2 α has been paid much attention by researchers as an essential component of the initiation of AA metabolism. The activation of cPLA 2 α is tightly regulated by Ca 2+ and phosphorylation. The Ca 2+ -independent PLA 2 (iPLA 2 ) family contains two enzymes and may play a major role in phospholipid remodeling. The platelet-activating factor (PAF) acetylhydrolase (PAF-AH) family contains four enzymes that exhibit unique substrate specificity toward PAF and/or oxidized phospholipids. Degradation of these bioactive phospholipids by PAF-AHs may lead to the termination of inflammatory reaction and atherosclerosis.