For clinicians plasma C-reactive protein (CRP) levels are the only widely available tests that provide a tangible link between inflammation and atherosclerosis. New AHA/CDC joint guidelines from 2002-03 now include the measurement of CRP as a class IIa recommendation for stratifying patients with known cardiovascular disease (CVD) at a moderate (10-20%) 10-year event risk and a class IIb recommendation for patients without known CVD [1]. While the association of CRP and atherosclerosis is by now accepted, the molecular biology behind the association is evolving rapidly into a fascinating story. While some of the story remains obscure, this review aims to bridge the clinical and basic science and identify what is known about the role of this ancient molecule in atherosclerosis. The review covers CRP's interaction with atherosclerosis' major ingredients and cell types including the endothelium, monocytes and neutrophils, lipoproteins and the complement system. Taken together, the clinical and basic science leave the tantalizing impression that CRP has a fundamental role in atherogenesis, and hint at a more complex immunomodulatory effect which transforms the acute inflammatory response to vascular injury into the chronic inflammation seen in atherosclerosis.