Systemic lupus erythematosus (SLE) is associated with an increase in the risk of premature cardiovascular complications caused by accelerated atherosclerosis, which significantly contributes to morbidity and mortality. Standard Framingham risk factors seem to be less important predictors of cardiovascular events than the presence of active SLE, and the immune dysregulation characteristic of lupus seems to play a dominant role in atherogenesis. Although both SLE-specific and nonspecific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. This review summarizes some of the proposed mechanisms that may promote accelerated vascular damage in lupus and explores potential targets for cardiovascular risk prevention in this patient population.