The anticardiolipin (aCL) antibody test was first established in 1983, using cardiolipin (negatively charged phospholipid) as an antigen in a solid-phase immunoassAy. It was first applied to the study of systemic lupus erythematosus patients, and was found associated with thromboses and recurrent pregnancy losses. The wide use of this test was determinant in the definition of the "aCL or antiphospholipid syndrome" (APS).Later, it was demonstrated that aCL antibodies do not recognize anionic phospholipids but are directed against plasma proteins bound to anionic phospholipids, mainly beta-2-glycoprotein I, which is now considered as the autoantigen in APS. Anti-beta-2-glycoprotein I (anti-beta2GPI) is not yet accepted as a serological criterion for APS, but most investigators would consider a patient with anti-beta2GPI antibodies and clinical features of APS to have the syndrome. aCL and anti-beta2GPI are a heterogeneous group of antibodies with different clinical significances and can be present in different autoimmune diseases as well as in infectious diseases.