Elucidation of the antibodies and antigens involved in the antiphospholipid syndrome has provided many new insights and research opportunities. The major autoantibodies associated with the syndrome and detected in clinical laboratory assays for antiphospholipid antibodies are directed against prothrombin and beta2-glycoprotein I beta2GPI), a phospholipid-binding plasma protein whose physiological function is unknown. Recent advances in our understanding of these antibodies and antigens include discovery of the crystal structure of beta2GPI, identification of a plasmin cleavage site in beta2GPI, genetic studies of beta2GPI polymorphisms, development of clinical laboratory assays using purified protein antigens, and the identification of antigen specific T cells.