Anti-annexin A5 antibodies are directed against annexin A5 - a phospholipid-binding protein that belongs to the ubiquitous annexin family. These antibodies were first discovered in 1994 by Matsuda et al. in women with recurrent fetal loss or preeclampsia and in patients with systemic lupus erythematosus and positive lupus anticoagulant and/or anticardiolipin antibodies. Since then anti-annexin A5 antibodies have been the focus of research. In addition to their well known prothrombotic and procoagulant activities the authors discuss the involvement of these antibodies in the pathogenesis of antiphospholipid syndrome, recurrent pregnancy loss, systemic lupus erythematosus and other immune and non-immune disorders. Controversial reports are presented and a possible interpretation of the results is given. The authors suggest the significance of anti-annexin A5 antibodies as an additional diagnostic marker and discuss the necessity of more extensive research on their clinical significance.