Atherosclerosis is an inflammatory disease that can be assessed by circulating biomarkers. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme produced in atherosclerotic plaque and is bound to low density lipoprotein and high-density lipoprotein cholesterol. It has a role in the pathogenesis of atherosclerosis by promoting vascular inflammation. It is emerging as a vascular-specific marker and predictor of risk for cardiovascular disease (CVD) events. Increasing evidence from many prospective epidemiologic studies have shown that elevated levels of Lp-PLA2 are associated with future CVD events. Measurement of Lp-PLA2 in individuals may provide clinically relevant information about their future risk of CVD events. Pharmacologic therapies and/or risk factor modification could be initiated after identification of individuals at risk for CVD. This review provides an overview of the pathophysiology, epidemiologic evidence, and clinical utility of Lp-PLA2.