The term "antiphospholipids" (aPLs) refers to an heterogeneous family of antibodies diagnosed either by clotting tests: the lupus anticoagulants or by Elisa: anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2GP1) especially. aPLS recognize phospholipids, alone or bound to plasma protein cofactor(s), or the cofactors themselves. aPLs have long been described in autoimmune diseases such as SLE, but may also be found in other clinical settings including infections, malignancies and drug administration. Their persistent presence can be associated with venous and/or arterial thrombotic complications and/or recurrent miscarriage, thus defining the "antiphospholipid syndrome" (APS). The heterogeneity of aPLs makes a comprehensive approach to laboratory investigation essential. Detection of lupus anticoagulants relies on increased clotting times in phospholipid-dependent tests. Their 4 step diagnosis includes: 1) screening (by at least two different tests); 2) demonstration of an inhibitory activity; 3) evidence of its phospholipid dependence; 4) exclusion of an associated coagulopathy. Among the aPLs detected by Elisa, IgG aCL are the most frequently investigated. However, other antibodies may represent useful biological tools. Among them, anti-beta2GP1 are thought to be more closely associated with a history of thrombosis than aCL and testing for anti-beta2 GP1 should now be systematically included in the biological diagnosis of APS. The Elisa used for aCL and anti-beta2GP1 are not fully standardized, and a number of methodological parameters may account for the interlaboratory discrepancies often observed. The clinical importance of other antibodies such as antiphosphatidylethanolamine, antiprothrombin or antiannexin V is being evaluated. An appropriate laboratory investigation of APS should, in all cases, combine the use of clotting and immunological assays, and assess the persistence of autoantibodies over time.