Cardiovascular disease (CVD) is multifactorial in etiology. Traditional cardiovascular risk factors, such as increased cholesterol concentrations and blood pressure, are used to assess CVD risk. Recently, better understanding of the role of inflammation in atherosclerosis has prompted many to propose the measurement of various inflammatory markers to better identify those who are at increased risk. C-reactive protein (CRP) is found in endothelial atherosclerotic lesions, and evidence suggests that it may play a role in atherogenesis. Of candidate serum markers that might add information to clinical risk assessment, high-sensitivity C-reactive protein (hsCRP) measurement has the most potential for clinical use for multiple reasons: (a) high hsCRP is associated with a twofold to a threefold increase in the prevalence of myocardial infarction, stroke, and peripheral vascular disease, and it predicts incident cardiovascular events in those with and without preexisting CVD; (b) the increased risk associated with high hsCRP is independent of other established risk factors; (c) hsCRP augments the predictive capacity of the Framingham Risk Score; (d) hsCRP assays are standardized, and this analyte is biologically stable over time; (e) various risk-reducing interventions also reduce hsCRP, and research is underway to assess whether specifically targeting hsCRP reduces CVD risk. National guidelines regarding the clinical utility of hsCRP in primary and secondary prevention settings have been recently issued.