With the current understanding that atherosclerosis is an inflammatory disorder, markers of the associated systemic inflammatory response have been extensively studied as predictors of cardiovascular disease. Recently the use of high-sensitivity C-reactive protein (hsCRP) has been proposed for risk assessment in individuals at intermediate risk of coronary heart disease. The traditional view of inflammatory biomarkers, including CRP, regards them as risk markers rather than risk factors. Either category of marker would serve a diagnostic role, monitor disease activity, and indicate the efficacy of therapy or changing prognosis. However a risk factor with a causal role would be a potential target for therapy. This review discusses the available evidence that argues for and against a causal role for inflammatory biomarkers, with specific reference to CRP, in the atherosclerotic process.