Antiphospholipid antibodies are a wide ranging, heterogeneous family of autoantibodies, formerly believed to be directed to anionic phospholipids. Recent research, however, has confirmed that they are directed to plasma proteins bound to suitable (phospholipid) anionic surfaces. The most well-known and best characterized antigens are beta 2-glycoprotein I, recognized by anticardiolipin antibodies, and prothrombin, recognized by most lupus anticoagulants. Lupus anticoagulants are generally identified on the basis of their capacity to prolong the phospholipid-dependent coagulation tests. Two types of lupus anticoagulants, anticardiolipin-type A, and antiprothrombin antibodies, whose presence is associated with different coagulation profiles, have been identified. Anticardiolipin-type A and antiprothrombin antibodies may be detected also by specific immunoassays. The capacity of several methodologies to detect antiphospholipid antibodies reflects chiefly their immunological and functional heterogeneity. Since most of the laboratory methods have not yet been standardized, the results of studies on the clinical relevance of antiphospholipid antibodies must be analyzed with caution. The association between antiphospholipid antibodies with peculiar clinical manifestations such as venous and arterial thrombosis, recurrent miscarriage, and thrombocytopenia, characterizes the so-called "antiphospholipid syndrome". Retrospective and cross-sectional studies have confirmed the role of anticardiolipin antibodies and lupus anticoagulants as risk factors for both venous and arterial thrombosis, the most common clinical manifestations of the antiphospholipid syndrome. Prospective studies performed in different patient populations have confirmed the association between anticardiolipin antibodies and lupus anticoagulants with venous, and possibly, arterial thrombosis, although information on the predictive value of the various laboratory tests with respect to thrombosis is still limited. It is hoped that the development and standardization of assays that selectively identify antiphospholipid antibodies associated with increased risk of thrombosis will lead to therapeutic strategies able to prevent thromboembolic complications of the antiphospholipid syndrome.