The antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in association with the persistent presence of autoantibodies called antiphospholipid antibodies (APAs). APAs are a heterogeneous group of circulating autoantibodies that can be detected either by phospholipid-dependent coagulation test for lupus anticoagulant (LA) or ELISA test for anticardiolipin and anti-β2GPI antibodies. In 2006, the revised criteria for the diagnosis of APS introduce the anti-β2GPI antibodies as a new biological criterion and highlight the necessity to increase the interval between two positive APA test from 6 to 12 weeks. However, despite these updated criteria, the diagnosis of APS remains challenging and we proposed here to make an overview of the latest evolution in the diagnosis of this syndrome.