Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis, the major underlying cause of CVD. In patients with systemic autoimmune diseases, it has been shown that traditional risk factors for CVD cannot completely explain the prevalence of atherosclerosis. Therefore, in addition to these traditional factors, nontraditional risk factors are suggested to contribute to atherogenesis. All risk factors, traditional and nontraditional, contribute to endothelial activation that, followed by endothelial dysfunction, is seen as one of the first steps in this process. This review updates information on the factors that contribute to accelerated atherosclerosis in patients with systemic autoimmune diseases, such as disease-related factors, inflammatory mediators, and advanced glycation end products.