Lupus anticoagulants (LAs) are a laboratory representation of the clinical syndrome of antiphospholipid syndrome (APS), and can also arise in other pathological states. Laboratory testing for LA is complex and three separate recent guidelines have been published. One test, the Russell viper venom time (RVVT), is the mandated laboratory test for inclusion in LA identification/exclusion in all three guidance documents. This is because the the RVVT is recognized to have great sensitivity for LA, with this generally recognized to be greater than that of most other LA screening assays. However, the RVVT is also very sensitive to the presence of many anticoagulant drugs, which diminishes its specificity for LA. Various strategies can be used to improve LA specificity and reduce anticoagulant assay interference.