Atherosclerosis is recognized as the pathological basis of cardiovascular disease (CVD) and recent advances in basic science have shown that it should be considered as a chronic inflammatory process. Both elements of the innate and the adaptive immunity appear to be actively involved in atherogenesis. In fact, the potential role played by pattern-recognition receptors (Toll-like receptors and scavenger receptors), cytokines (such as IL-1, IL-6, TNFalpha), chemokines and pentraxines (such as CRP and PTX3) represents an emerging field of investigation in atherogenesis. In the near future we expect a better definition of the real biological and clinical impact on CVD of these mediators. On one side, they could become useful to complement traditional risk factors, in order to identify new categories of subjects prone to CVD development. On the other, they could become an additional potential target for therapeutic strategies.