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Patients without traditional cardiovascular risk factors continue to suffer from cardiovascular events, which has prompted a search for novel markers to better assess cardiovascular risk. Inflammatory biomarkers have surfaced as prime candidates, given the integral role of inflammation in atherosclerosis. C-reactive protein (CRP) measurements in particular have emerged as powerful predictors of cardiovascular risk in a broad spectrum of patient populations. Newer high sensitivity CRP assays now in use are standardized and reproducible, and can detect variations in CRP below the limit of standard assays. In primary prevention populations, studies have shown up to a 2–4-fold increased risk of cardiovascular events in healthy patients with elevated CRP levels. In this population, models incorporating CRP and lipid parameters appear to predict risk significantly better than lipids alone. In patients with established cardiovascular disease and in patients undergoing percutaneous coronary interventions, CRP levels may help predict short- and long-term prognosis, identifying subgroups of patients at increased risk of recurrent events. CRP levels may also prove useful in targeting therapy for primary and secondary prevention, by identifying patients who would most benefit from medications such as statins and aspirin. This review presents an overview of the data regarding CRP measurement for cardiovascular risk assessment.