In the past several years, evidence has accumulated that factors other than conventional risk factors may contribute to the development of atherosclerosis. Conventional risk factors predict less than one half of future cardiovascular events. Furthermore, conventional risk factors may not have the same causal effect in different ethnic groups in whom novel risk factors may have a role. These newer risk factors for atherosclerosis include homocysteine, fibrinogen, impaired fibrinolysis, increased platelet reactivity, hypercoagulability, lipoprotein(a), small dense low-density lipoprotein cholesterol, and inflammatory-infectious markers. Identification of other markers associated with an increased risk of atherosclerotic vascular disease may allow better insight into the pathobiology of atherosclerosis and facilitate the development of preventive and therapeutic measures. In this review, we discuss the evidence associating these factors in the pathogenesis of atherosclerosis, the mechanism of risk, and the clinical implications of this knowledge.