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Cardiolipin is a key mitochondrial membrane phospholipid involved in the regulation of generation of ATP. Cardiolipin synthesis and remodeling are tightly regulated processes in eukaryotic cells. The role of phospholipases in the regulation of cardiolipin metabolism is becoming much clearer. Cardiolipin is hydrolysed by several classes of phospholipases including calcium-independent phospholipase A2, secretory phospholipase A2, and cytosolic phospholipase A2. Mitochondrial calcium-independent phospholipase A2 gamma has emerged as a key player not only in the regulated hydrolysis of cardiolipin to monolysocardiolipin, but also in the overall regulation of mitochondrial function and energy production. The purpose of this chapter is to summarize some of the more current findings on the role of phospholipases in the regulation of cardiolipin metabolism in the heart and mammalian tissues. In addition, a brief discussion on the role of exogenous phospholipase-treatment of cells on cardiolipin metabolism is presented. [ABSTRACT FROM AUTHOR]