The purpose of this article is to review the evidence concerning the utility of lipoprotein-associated phospholipase A2 (Lp-PLA2), a key promoter of vascular inflammation, as a biomarker of future risk of cardiovascular disease. In addition, the evidence of complementary action of Lp-PLA2 and C-reactive protein (CRP) is evaluated. On balance, there is a great deal of consistency across studies supporting Lp-PLA2 as a risk factor for coronary disease and ischemic stroke (independently of traditional risk factors and CRP) among persons with and without clinical coronary artery disease. On the other hand, there is yet limited and inconsistent evidence for a synergistic effect of Lp-PLA2 and CRP on cardiovascular disease risk. Additional studies are thus needed before widespread Lp-PLA2 and CRP testing with regard to incremental cardiovascular disease risk prediction can be recommended.