In an attempt to improve global cardiovascular risk prediction, considerable interest has focused on C-reactive protein (CRP), that has been shown in multiple prospective epidemiological studies to predict incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death. CRP is a hepatically-derived pentraxin that plays a key role in the innate immune response. Standard CRP tests determine levels which are increased up to 1000-fold in response to infection or tissue destruction, but cannot adequately assess the normal range. High-sensitive CRP detects levels of CRP within the normal range as well as higher levels proven to predict future cardiovascular events. The relationship between a patient's baseline plasma level of CRP and future vascular risk has been consistent in several studies, and in most cases has proven independent of major "traditional" risk factors such as age, smoking, cholesterol levels, blood pressure and diabetes. Several pharmacological agents proven to reduce vascular risk influence CRP levels. Other lipid-lowering agents reported to reduce CRP include niacin, fibrates, and gemfibrozil. Aspirin also has an intriguing interaction with CRP in that the magnitude of relative risk reduction attributable to aspirin in primary prevention appears to be greatest among those with elevated CRP and declines proportionately in direct relation to CRP levels. Observational data, moreover, suggest possible differential benefits for clopidogrel and abciximab on the basis of CRP levels before percutaneous coronary interventions. As documented above for primary prevention, CRP is an independent predictor of future cardiovascular events that adds prognostic information to lipid screening, to the metabolic syndrome, and to the Framingham risk score. An approach in primary prevention is to measure CRP only among those at intermediate risk as defined by the Framingham risk score. In secondary prevention, the potential utility of CRP is less certain, as aggressive therapies should already be instituted and low-density lipoprotein evaluation provides an excellent method to assess statin efficacy.