Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Inhibition of PLA(2) alters cancer cell growth and death in vitro and PLA(2) expression is increased in breast, lung, and prostate cancers compared to control tissues. Thus, PLA(2) may be novel targets for chemotherapeutics. However, PLA(2) are a diverse family of enzymes, encompassing 19 members. The selectivity of these individual PLA(2) for phospholipids varies, as does their location within the cell, and tissue expression. Thus, their role in cancer may also vary. This review summarizes the expression of individual PLA(2) in cancers, focuses on the potential mechanisms by which these esterases mediate carcinogenesis, and suggests that select PLA(2) isoforms may be targets for anti-cancer drugs.