Recent advances in basic science have shown that atherosclerosis should be considered as a chronic inflammatory process, and that a pivotal role of inflammation is evident from initiation through progression and complication of atherosclerosis. In the past few years many studies have examined the potential for biochemical markers of inflammation to act as predictors of coronary heart disease (CHD) risk in a variety of clinical settings. Several large, prospective epidemiological studies have shown consistently that C-reactive protein (CRP) and interleukin-6 (IL-6) plasma levels are strong independent predictors of risk of future cardiovascular events, both in patients with a history of CHD and in apparently healthy subjects. These molecules could be useful to complement traditional risk factors, as well as to identify new categories of subjects prone to atherosclerosis development. An intriguing question is whether these inflammatory molecules simply represent sensitive markers of systemic inflammation or if they actively contribute to atherosclerotic lesion formation and instability. In this paper we will review the evidence concerning the cardiovascular prognostic value and the potential direct involvement of CRP and IL-6 in atherogenesis.