In primary prevention, traditional risk factors are a useful first step in determining who is at cardiovascular risk, however, it has been noted that a considerable number of those at risk cannot be identified on the basis of traditional risk factors alone. Among blood biomarkers, C-reactive protein (CRP), measured by high-sensitivity assays (hsCRP), has received widespread interest and a large database has been accumulated on its potential role as a predictor of cardiovascular risk, although observed associations between circulating CRP and coronary heart disease (CHD) are unlikely to be causal, as recently indicated by various Mendelian randomization studies. In a meta-analysis of 22 prospective studies, the multivariable adjusted, combined odds ratio for CRP to predict CHD, comparing extreme tertiles, was 1.58 (95% confidence interval, 1.48-1.68). Several recent studies showed a significant contribution of CRP to coronary risk prediction independent of the Framingham Risk Score, with better discrimination, calibration and improved, albeit modest reclassification of subjects at risk. To test the hypothesis whether or not subjects with normal low-density lipoprotein cholesterol but elevated CRP represent a population at increased risk that might benefit from statin treatment, the JUPITER trial randomized 17,802 apparently healthy persons to either 20 mg rosuvastatin daily or placebo. Rosuvastatin significantly reduced the incidence of major cardiovascular events. The rates of the primary endpoint (composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, revascularization, and confirmed death from cardiovascular causes) were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively. Relative risk reduction was 44%. CRP may have more accurately selected high-risk subjects due to its association with very many risk factors, thus representing an integrative marker of the total inflammatory burden of an individual. JUPITER has revitalized the discussion on CRP in clinical practice and will make it more difficult in the future to neglect the evidence built around CRP and cardiovascular risk.