Several inflammatory mediators regulate the evolution of atherosclerosis. C-reactive protein (CRP) is an acutephase reactant, with a direct effect in inflammatory processes characterizing atherosclerosis. For this reason, CRP is actually considered as a factor, rather than simply a cardiovascular risk marker. The recent demonstration of CRP production not only by the liver, but also within atherosclerotic plaques by activated vascular cells, suggests a possible dual role, as both systemic and tissue molecule. Although more studies are needed, some therapeutic approaches to reduce CRP levels have been performed with encouraging results. Behavioral or pharmacologic interventions have been shown to reduce both CRP levels and the associated risk of cardiovascular acute events. Therefore, although most of national Cardiovascular Associations do not suggest high sensitivity CRP screening of the entire adult population as a public-health measure to stratify the cardiovascular risk, serum hs-CRP levels could be a promising target for therapies focused on reducing cardiovascular risk.