Antiphospholipid antibodies (aPL) comprise a heterogeneous group of antibodies directed against phospholipids and/or protein-complexed phospholipids. aPL are associated with the serious autoimmune condition 'antiphosholipid (antibody) syndrome' (APS) and can be defined by either 'solid-phase' assays that identify anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aB2GPI) or 'liquid-phase' assays that identify lupus anticoagulants (LAs). There is a lack of standardization associated with all forms of aPL testing; however, intermethod and interlaboratory variation using aCL and aB2GPI assays is generally higher than that for LA testing by dRVVT (dilute russell viper venom time) procedures. Compared with either aCL or aB2GPI, LA is also more strongly associated with clinically adverse findings of APS, including thrombosis and obstetric morbidity. This review explores the potential reasons for the above findings and concludes that ultimately a more holistic approach to aPL/APS investigations is needed.