Patients with chronic inflammatory disorders are at increased risk of developing premature cardiovascular disease. Despite significant advances in our understanding of the effects of inflammatory pathways on the vasculature, clear guidelines on the management of traditional and nontraditional cardiovascular risk factors in patients with systemic autoimmunity are lacking. Thus, rigorous studies assessing the individual contributions of the various treatments used in autoimmune disorders, as well as their effects on atherosclerosis development in these conditions, are needed. Furthermore, effective screening methods are needed to identify those patients with inflammatory disease who are at the highest risk for atherosclerotic complications, and who would benefit from early intervention. There is a clear need for a unifying explanation of the factors that promote premature cardiovascular disease in patients with chronic inflammatory disorders. Nevertheless, ongoing advances in the understanding of immune-mediated vascular damage mean that we are edging closer to the development of disease-specific preventive strategies to ameliorate or abrogate premature cardiovascular disease in these patients.