The antiphospholipid syndrome is characterized by arterial and venous thrombosis, as well as pregnancy morbidity, in the presence of elevated levels of antiphospholipid antibodies. These autoantibodies have procoagulant activity, as they affect platelets, humoral coagulation factors, and endothelial cells. In addition, they are proatherogenic, as demonstrated by animal models and by the increased prevalence of cardiovascular diseases in patients with systemic lupus erythematosus and antiphospholipid syndrome. Moreover, antiphospholipid antibodies, including anticardiolipin, anti-b2-glycoprotein-I, and anti-oxidized low-density lipoprotein, are associated with atherosclerosis and its consequences in the general population as well. This autoimmune aspect of atherosclerosis in the presence or absence of an autoimmune disease suggests benefit from development of immunomodulating therapies.