The inflammatory nature of atherosclerosis has long been postulated, and though currently widely accepted, the concept is difficult to disseminate and to translate into concrete public health measures. Through the years, it has been discerned that low density lipoprotein (LDL) cholesterol serves as the stimulus for the inflammatory response when it is deposited into the subendothelium. LDL stimulates the migration of the inflammatory cells into the subendothelium; a sequelae of cellular immune responses and a cascade of cytokines ensue, eventually resulting in the formation of a vulnerable plaque. Inflammatory cells, particularly macrophages and lymphocytes, and their cytokines play a role in all stages of the atherosclerotic process, modulating the vascular remodeling process as more LDL cholesterol is absorbed into the subendothelial space and forms an ever enlarging lipid core. When inflammatory cells release metalloproteinases into the fibrous cap separating the lipid core from the lumen, plaque becomes vulnerable to rupture especially with increased shear stress from luminal blood flow resulting in thrombosis; clinically acute coronary syndromes become manifest. The role of mast cells, macrophage apoptosis, and the role of the vasa vasorum in plaque progression has recently been delineated. Pharmacologic intervention to aggressively lower LDL cholesterol culminated in the discovery of statins which were proven in large landmark trials to lower the morbidity and mortality associated with the atherosclerotic process. Several generations of statins have evolved; however, residual mortality is observed despite aggressive therapy. A recent trial showing the beneficial effects of statins in patients with acceptable or normal lipid profiles but with elevated high sensitivity C reactive protein (hsCRP) augurs a change in the paradigm of treatment for atherosclerosis. Inflammatory biomarkers such as hsCRP and lipoprotein-associated phospholipase A2 (Lp-PLA2) are anticipated to change guidelines and treatment algorithms, and public health policy. The implication of infectious processes as triggers of inflammation in the atherosclerotic process is also discussed, particularly the role of periodontal disease, the role of flu vaccination, and the role of bacteria such as Chlamydia and Helicobacter.