Chronic inflammatory diseases including atherosclerosis are major causes of morbidity and mortality worldwide. However, the factors, which trigger processes that determine the outcome of an inflammatory response, are still poorly understood. Accumulating evidence suggests that certain lipid oxidation products, such as oxidized phospholipids (OxPL), may represent endogenously formed factors that are capable of triggering vascular inflammation. This review will address important questions regarding mechanisms involved in acute and chronic inflammation, and discuss the role of OxPL as key players in triggering the inflammatory response in atherosclerosis. Better understanding of how OxPL contribute to vascular inflammation should lead to new strategies in the treatment of chronic inflammatory disorders.