Recent research has focused on the use of high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, in the detection of patients at increased risk for cardiovascular disease. Several prospective studies have demonstrated that hs-CRP is an independent predictor of future risk for cardiovascular events among healthy individuals, as well as among patients with acute coronary syndromes. In addition, because half of all cardiovascular events occur in persons with low to average levels of low-density lipoprotein cholesterol, hs-CRP may aid in identifying patients at high risk for a first cardiovascular event who might otherwise be missed by lipid screening alone. Thus, hs-CRP is a potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. The Centers for Disease Control and Prevention and the American Heart Association have therefore proposed joint guidelines for the use of hs-CRP in determining cardiovascular disease risk. The author reviews numerous studies examining the prognostic value of hs-CRP and outlines ongoing efforts to assess the effect of statin therapy in healthy individuals with low levels of low-density lipoprotein cholesterol and high levels of hs-CRP.