Patients with systemic lupus erythematosus have a significantly increased risk of cardiovascular events due to atherosclerosis. Traditional cardiac risk factors cannot fully explain this increased risk. Recent evidence strongly suggests that atherosclerotic plaque is largely driven by inflammation and an active immunological response, in contrast to the long-held belief that plaque is a passive accumulation of lipids in the arterial wall. Current approaches to the prevention of atherosclerosis in systemic lupus erythematosus involve targeting modifiable cardiac risk factors. Future preventive strategies may include therapies that counteract the immunologic responses that lead to plaque formation.