The antiphospholipid syndrome (APS), also known as “Hughes syndrome”, is characterized by typical clinical features such as arterial/venous thromboses or recurrent miscarriages together with persistently positive tests for antiphospholipid antibodies. The criteria for classification of the APS have been revised in 2004 in Sydney. Besides the clinical criteria, three different laboratory tests are listed: lupus anticoagulant, anticardiolipin antibodies (IgG and IgM) and anti-β2-Glycoprotein I antibodies (IgG and IgM). The latter was not included in the former Sapporo criteria. However, by majority, the Sydney committee agreed that they are an independent risk factor for thrombosis and pregnancy complications. For APS diagnosis, β2-Glycoprotein I antibody tests show higher specificity than anticardiolipin assays. In 3-10% of APS patients, β2-Glycoprotein I antibodies may be the only positive test. The association of β2-Glycoprotein I antibodies with pre-eclampsia and/or eclampsia in unselected pregnant women who tested negative for anticardiolipin antibodies implies that the inclusion of β2-Glycoprotein I antibodies may also help clarify this type of pregnancy morbidity. Outside the context of clinical studies, testing for β2-Glycoprotein I antibodies can be helpful for APS diagnosis, particularly when anticardiolipin antibodies and lupus anticoagulant are negative and APS is strongly suspected.