The laboratory detection of factor VIII inhibitors is invariably performed by methods that measure the inactivation of factor VIII in mixtures of test plasma and exogenous factor VIII, e.g. normal pooled plasma. Unfortunately the intra- and inter-laboratory variation of the inhibitor assays is rather high often resulting in unreliable results. The pH of the mixtures of test plasma and pooled plasma, incubation time and temperature, type of control sample, von Willebrand content of factor VIII deficient plasma that is used in the assay and the presence of lupus anticoagulant all influence and/or interfere with the results of inhibitor testing. In this review these assay characteristics, pitfalls and limitations of the assays are discussed.