Phospholipase A₂ (PLA₂) enzymes catalyze the hydrolysis of the sn-2 position of glycero-phospholipids to liberate free fatty acids and lysophospholipids. More than one third of the PLA₂ enzymes belong to the secreted PLA₂ (sPLA₂) family, which contains 11 isoforms. Individual sPLA₂s exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Since sPLA₂s are secreted, their target membranes should reside in the extracellular spaces. In comparison with the well-established roles of cytosolic PLA₂, the biological roles of sPLA₂s have remained unclear until recently. However, recent studies using transgenic and knockout mice for several sPLA₂ enzymes have revealed their distinct contributions to various biological events by producing lipid mediators, by promoting membrane remodeling, by modifying extracellular non-cellular lipid components such as surfactants and lipoproteins, or by degrading foreign phospholipids such as bacterial membranes and dietary lipids. In this review, emerging biological roles of sPLA₂ enzymes in pathophysiology will be discussed.