Atherosclerosis constitutes the underlying disease to the clinical manifestations of myocardial infarction, stroke, and gangrene. Despite the success of statins, prevention of clinical events of atherosclerosis remains a major challenge in current-day cardiology. Research into the inflammatory nature of atherosclerosis has led to improved mechanistic understanding of its pathogenesis and to the identification of novel therapeutic targets discussed in this review. Recent genetic and epidemiological data document shared pathologies of chronic inflammatory diseases and atherosclerosis. Anti-inflammatory treatment regimens used in these diseases, including tumor necrosis factor-α blockade, IL-1 receptor antagonism, and leukotriene blockade may be beneficial also in patients with coronary artery disease. Enhancing inherent atheroprotective immunity by expansion of regulatory T cells may emerge as a future therapeutic strategy. Immunization strategies directed against atherosclerosis-related antigens such as epitopes within the low-density lipoprotein particle have been extensively studied in animal models and may enter the clinical stage. Success of these novel therapies will be critically dependent on the adequate identification of patients and choice of appropriate clinical endpoints.