Antiphospholipid antibodies are a wide and heterogeneous group of immunoglobulins that include, among others, lupus anticoagulants and anticardiolipin antibodies. Their presence in patients with arterial and venous thrombosis, and/or obstetrical complications, defines the antiphospholipid syndrome. Antiphospholipid antibodies do not recognize anionic phospholipids, but recognize plasma proteins bound to suitable anionic surfaces: beta2-glycoprotein I and prothrombin are the most common and most frequently investigated antigens. We systematically reviewed published articles on the antiphospholipid syndrome to investigate the association between thrombosis and some antiphospholipid antibodies. Lupus anticoagulants were a clear risk factor for thrombosis, irrespective of the site and type of thrombosis, the presence of systemic lupus erythematosus, and the methods used to detect them. Anticardiolipin and anti-beta2-glycoprotein I antibodies were possible risk factors of thrombosis, at least in some selected situations. The measurement of antiprothrombin antibodies is not helpful to define the patient's risk of thrombosis. These results are mainly due to the still far from optimal standardization of the methods to detect antiphospholipid antibodies; the lack of standardized reference materials; the heterogeneity in reagents, calibrators, and assay conditions; and the methods used to calculate the results. Many efforts are currently being made to improve assay standardization and harmonization, which should help to clarify the clinical relevance of antiphospholipid antibodies.