Lupus anticoagulants are autoantibodies that are associated with an increased risk of thromboembolic events and adverse pregnancy outcomes. They are identified by a systematic, laboratory-based approach that includes the following steps: 1) prolongation of a phospholipid-dependent screening assay, 2) demonstration of an inhibitory activity by mixing studies with healthy pooled plasma, and 3) documentation that the inhibitory activity is phospholipid dependent. Laboratory testing can be complicated by several variables, however, including preanalytical factors, multiple reagents and testing platforms, and difficulties with interpreting the results. Guidelines have been developed through several professional organizations that build upon the steps listed above and provide guidance to improve the reproducibility of test results. This article reviews the guidelines developed by the Lupus Anticoagulant/Phospholipid Dependent Antibodies Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis and addresses several common issues encountered during testing for these clinically relevant autoantibodies.