Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+ CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the 'culprit' plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.