Biomarkers are generally considered to be plasma measurements of molecules, proteins, or enzymes that provide independent diagnostic and prognostic value by reflecting an underlying disease state or condition. In the case of coronary heart disease, they must reflect the underlying biology of the vessel wall and in particular, the atherosclerotic process and/or its sequelae. The clinical utility of a biomarker depends on its ability to account for a significant proportion of the disease being evaluated; it should be accurate and reliable; provide good sensitivity and specificity; and be available for widespread application. Data are being accumulated on the potential clinical utility of markers of inflammation, hemostasis and thrombosis, phospholipases, proteolysis and oxidative stress. Whereas C-reactive protein (CRP) emerges as a biomarker in the setting of primary prevention, we have recently found that CRP enhances the endothelial expression of metalloproteinases (MMPs). Regardless of the causality, circulating inflammatory markers have the potential to refine prediction of risk of cardiovascular events. However, a recommendation that they should be added to current risk factor scores is premature, since the benefits and costs of screening with any inflammatory marker require careful evaluation. A multimarker approach to estimate cardiovascular risk either by inflammatory markers and cumulative risk markers obtained from non-invasive tests or both may be superior to assessing a single marker.