Overwhelming evidence spanning three decades has consistently shown that coronary artery disease is a major cause of morbidity and mortality in Systemic Lupus Erythematosus. Traditionally this was explained by abnormalities of the lipid profile induced by prolonged steroid treatment. Subsequently, antiphospholipid antibodies were presented as an additional cardiovascular risk factor. Recently, antibodies towards high-density lipoprotein and antiapolipoprotein A-I have been identified. These, together with anti-beta2 glycoprotein-1, interfere with the major antioxidant defence of patients with SLE and with primary antiphospholiqid syndrome exposing them to the atherogenic potential of enhanced oxidative stress. The present review discusses how the latter auto-antibodies, together with abnormalities of their target lipid auto-antigens, could enhance the risk of atherosclerosis in SLE and APS.