C-reactive protein (CRP), formerly considered solely an excellent biomarker of inflammation, is now viewed as a direct contributor in atherosclerosis. With the advent of high-sensitivity assays for determining CRP, this protein has emerged as one of the most powerful independent predictors of cardiovascular disease. CRP level, which significantly increases in acute coronary syndromes, has a prognostic value in cardiovascular risk not only in patients with cardiovascular complications, but also in apparently healthy individuals. The in vivo mechanisms of CRP as a mediator of the inflammatory state and thrombotic complications are continuing to be unraveled. Here we focused on the role of C-reactive protein in the pathophysiology of atherosclerosis, including the potential mechanisms of CRP's action in the circulation, as well as the potential contribution of genetic variations within the CRP gene in the pathophysiology of vascular complications.