The presence of lupus anticoagulants (LA) in plasma alone or in combination with solid-phase antiphospholipid antibodies is an important prerequisite to define the antiphospholipid syndrome. The lack of specific tests to identify LA prompted standardization authorities to define a set of diagnostic criteria based on indirect evidence of the presence of LA and defined as screening, mixing and confirmatory studies. Accordingly, these studies must be carried out on patient plasmas and the relevant criteria satisfied before a firm diagnosis of LA can be made. Clinicians involved in LA testing should be aware of the limits which are inherent to this diagnosis, especially in patients who at the time of testing are on heparin and/or oral anticoagulant treatment, or are close to the acute thrombotic event. This article is aimed at reviewing the current situation and the light and shadows associated with this diagnostic procedure.