The classical acute-phase protein, C-reactive protein (CRP), is an exquisitely sensitive systemic marker of disease with broad clinical utility for monitoring and differential diagnosis. Inflammation, the key regulator of CRP synthesis, plays a pivotal role in atherothrombotic cardiovascular disease. There is a powerful predictive association between raised serum CRP values and the outcome of acute coronary syndromes, and, remarkably, between even modestly increased CRP production and future atherothrombotic events in otherwise healthy individuals. Baseline CRP values also reflect metabolic states associated with atherothrombotic events. The presence of CRP within most atherosclerotic plaques and all acute myocardial infarction lesions, coupled with binding of CRP to lipoproteins and its capacity for pro-inflammatory complement activation, suggests that CRP may contribute to the pathogenesis and complications of cardiovascular disease. We review the biological properties of CRP, the association between CRP and cardiovascular disease, and the possibility that CRP may be a novel therapeutic target.