C-reactive protein (CRP) is a marker of systemic inflammation, and it has been implicated in the pathogenesis of many chronic diseases, including cardiovascular (CV) diseases. With highly sensitive CRP assays, serum CRP can add considerably to standard coronary heart disease risk factors and in the prediction of subsequent major CV risk. We review evidence supporting the assessment of highly sensitive CRP both in patients with established CV diseases and in those without known disease as well as evidence supporting CRP as a target of therapy. We also review various pharmacologic (especially intensive statin therapy) and nonpharmacologic therapies to reduce levels of CRP.