Lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)), a member of the phospholipase superfamily, circulates primarily bound to low-density lipoprotein and has been associated with cardiovascular disease risk in epidemiologic studies. However, it has not been established whether Lp-PLA(2) is a risk marker or a risk factor. Identification of individuals with elevated Lp-PLA(2) may improve risk assessment, and Lp-PLA(2) may also provide an additional target of therapy. Statin therapy has been shown to reduce Lp-PLA(2), and selective inhibitors of Lp-PLA(2) are under development. Additional research is needed to further determine the role of Lp-PLA(2) in atherogenesis and atherothrombotic events.