The antiphospholipid (aPL) syndrome is an acquired autoimmune disorder of unknown etiology in which patients present with thrombosis together with laboratory evidence for antibodies in blood that recognize anionic phospholipid-protein complexes. The main antigenic target for the aPL antibodies has been identified to be &bgr;2glycoprotein I (&bgr;2GPI), a phospholipid-binding protein. The high affinity of aPL antibody-&bgr;2GPI complex for phospholipid membranes seems to be a critical step in the mechanism of this disease. This review focuses on some of the major mechanisms that have been proposed to explain this disorder.