Secretory phospholipase A₂ (sPLA₂) is a growing family of structurally related, disulfide-rich, low molecular weight, lipolytic enzymes with a His-Asp catalytic dyad. sPLA₂s are distributed in a wide variety of vertebrate and invertebrate animals, plants, bacteria, and viruses, and there are 10 catalytically active sPLA₂ isozymes in mammals. Although the structural bases for mammalian sPLA₂s have been well documented, their physiological functions are still subject to debate. Individual mammalian sPLA₂s have distinct enzymatic properties and display distinct tissue expression patterns, suggesting that each enzyme acts on distinct phospholipid membrane moieties in vivo. In this article, we briefly review our latest understanding of the possible physiological functions of sPLA₂s, in keeping with their diverse actions on mammalian and nonmammalian cell membranes.