Lipoprotein-associated phospholipase A2 (LP-PLA2) is an emerging inflammatory marker that is used to assess the risk for cardiovascular disease (CVD) and associated events. Several epidemiologic studies have demonstrated an independent association between plasma Lp-PLA2 concentration and risk for cardiovascular events. HMG-CoA reductase inhibitors (statins) and fenofibrates can reduce Lp-PLA2 concentrations in plasma, and orally active, specific Lp-PLA2 inhibitors have been developed and are in clinical trials to evaluate the potential of Lp-PLA2 as a therapeutic target. This article reviews recent studies of Lp-PLA2 in the setting of CVD, discusses the proposed mechanisms of action of Lp-PLA2, and describes methods for measurement and their clinical application. Recent evidence that suggests Lp-PLA2's potential usefulness as a therapeutic target also is reviewed.