Advances in vascular biology have shown that inflammation plays an integral role in the development of cardiovascular disease. Extensive study of high-sensitivity C-reactive protein (hs-CRP) has demonstrated that this measure of inflammation predicts cardiovascular risk not reflected by traditional risk factors, adds prognostic information to traditional risk assessment, and predicts long-term cardiovascular risk in individuals with no prior evidence of cardiovascular disease. Patients with elevated hs-CRP levels in the absence of elevated cholesterol appear to derive preventive benefit from statin therapy that is similar in magnitude to that in patients with elevated cholesterol. The large-scale Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosvastatin (JUPITER) trial represents a critical study to determine the utility of a strategy for targeting statin therapy to prevent incident cardiovascular disease in patients at increased cardiovascular risk on the basis of elevated hs-CRP who would not be considered candidates for therapy on the basis of hypercholesterolemia or traditional risk assessment. Inclusion of hs-CRP measurement in risk screening and use of this information to guide preventive therapy could result in a marked improvement in prevention of cardiovascular morbidity and mortality.