Atherosclerosis has traditionally been attributed to disordered cholesterol metabolism with associated accumulation of lipid substrate in the arterial wall. It is now believed that systemic and local inflammatory events mediate all phases of plaque development, progression, and degeneration. No longer regarded as a bland, mechanical process, plaque evolution is now best understood as a pitched battle between proinflammatory and anti-inflammatory cellular and molecular elements. Not unlike models of chronic wound healing or ischemia-reperfusion, the biologic state of a plaque at any given time is transient and mutable, reflecting a dynamic balance of numerous local and circulating inflammatory forces. Dreaded complications of the disease such as myocardial infarction and stroke result from acute shifts in this balance in favor of plaque instability and vulnerability over stable states of chronic inflammation. The purpose of this article is (1) to review the inflammatory pathogenesis of atherosclerosis on a molecular basis, (2) describe several of the emerging inflammatory biomarkers currently being investigated with particular interest in their possible roles as direct mediators of vascular disease, and (3) identify several important implications for diagnosis and therapy.