Phospholipase A₂ (PLA₂ catalyzes the hydrolysis of the sn-2 position of membrans glyerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs). The same reaction also produces lysophosholipids, which represent another class of lipid mediators. So far, at least 19 enzymes that posses PLA₂ activity have been identified in mammals. The secretory PLA₂ (sPLA₂) family, in which 10 isozymes have been identified, consists of low-molecular-weight, Ca²⁺-requring, secretory enzymes that have been implicated in a number of biological processes, such as modification of cicosanoid generation, inflammation, host defense, and atheroselecrosis. The cytosolic PLA₂ (cPLA₂) family consists of 3 enzymes, among which cPLA₂α plays an essential role in the initiation of AA metabolism. Intracellular activation of cPLA₂α is tightly regulated by Ca²⁺ and phosphorylation. The Ca²⁺, independent PLA₂ (iPLA₂) family contains 2 enzymes and may play a major role in membrane phospholipid remodeling. The platelet-activating factor (PAF) acetylhydrolase (PAF-AH) family represents a unique group of PLA₂ that contains 4 enzymes exhibiting unusual substrate specificity toward PAF and/or oxidized phospholipids. In this review, we will overview current understanding of the properties and functions of each enzyme belonging to the sPLA₂, cPLA₂, and iPLA₂, families, which have been implicated in signal transduction.