Considerable progress has been made recently in understanding the pathobiology of atherosclerosis. To a significant degree it is an inflammatory disease of the vessel wall. Progression of atherosclerosis or its stabilization reflects the tension between cytokines and effectors that play both an inhibiting and a facilitating role in the progression of atherosclerosis, including platelet-derived growth factor (PDGF), interleukin-1, tumor necrosis factor (TNF) -alpha, and MCP-1. The response to injury model remains central to our understanding of atherogenesis. Numerous factors may initiate endothelial injury, including mechanical factors (hypertension and high shear stress in the artery), homocysteine, oxidized low-density lipoprotein (LDL), possibly infectious agents such as Chlamydia, viruses, and toxins such as nicotine. These factors lead to endothelial cells' increasing expression of receptors for LDL and increased adherence of monocytes and macrophages and T cells. Progression of atherosclerosis can lead to the development of a plaque that is vulnerable to rupture and that would then produce an acute coronary syndrome. In addition to standard biomarkers and angiographic approaches for detecting plaque rupture, novel diagnostic approaches are under development, including near infrared spectroscopy, catheter-based thermography, and optical coherence tomography. Our better understanding of the atherosclerotic plaque provides multiple opportunities for interdicting arterial injury, and the response to it.