Phospholipase A2 (PLA2) 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 PLA2 activity have been identified and cloned in mammals. The secretory PLA2 (sPLA2) family, in which 10 isozymes have been identified, consists of low-molecular weight, Ca2+-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 PLA2 (cPLA2) family consists of three enzymes, among which cPLA2alpha has been paid much attention by researchers as an essential component of the initiation of AA metabolism. The activation of cPLA2alpha is tightly regulated by Ca2+ and phosphorylation. The Ca2+-independent PLA2 (iPLA2) 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.