Inflammation and dysregulated cholesterol metabolism are key components in the pathogenesis of atherosclerosis. Premature atherosclerosis is a characteristic feature of systemic lupus erythematosus. Although the cellular and molecular mechanisms underlying accelerated atherogenesis in lupus are not thoroughly understood, inflammation associated with the rheumatic disease state may promote atherosclerosis. Increasing evidence indicates that the systemic inflammatory load in lupus disrupts cholesterol homeostasis, increasing vulnerability to cholesterol accumulation in cells of the artery wall, including macrophages and endothelium. The relationship between the inflammatory state and dyslipidemia in lupus is complex, involving lipoproteins, cholesterol transporters, scavenger receptors, and oxysterols. The impact of lupus on each of these components of the cholesterol flux pathways is discussed. The formation of autoantibodies against epitopes within lipoprotein particles and their controversial role in atherogenesis is addressed.