Systemic lupus erythematosus (SLE) is a highly variable autoimmune disease characterized by aberrant host-immune responses and chronic inflammation. Recently, a strong association between cardiovascular (CV) disease and SLE has emerged. Thus, low serum, high-density lipoprotein strongly correlated with elevated erythrocyte sedimentation rate, IL-6, TNF-alpha and the SLE disease activity index after adjusting for age, gender, race, BMI, insulin sensitivity and any concurrent drug use. In SLE, CV disease is characterized by increased VEGF, which may alter vascular hemostasis and promote neoangiogenesis. Increased low-density lipoprotein-cholesterol and proinflammatory high-density lipoprotein-cholesterol uptake by monocytes together with enhanced low-density lipoprotein-cholesterol oxidation results in the deposition of altered cholesterol forms into the vascular wall. This contributes to precocious and accelerated development of coronary artery plaques. Cholesterol-reducing drugs should be considered in the standard of care of SLE patients, especially in those with an unfavorable CV disease risk profile, which could reduce the probability of atherosclerosis progressing to CV disease or stroke in these patients.