The development of factor VIII (FVIII) inhibitors in haemophiliac patients following therapeutic administration of exogenous FVIII is one of the major factors complicating the treatment of this disease. Most FVIII inhibitors described to date appear to be directed towards epitopes involved in the procoagulant activity of FVIII. However, recent data suggest that some FVIII inhibitors may behave as catalytic antibodies, able to cleave FVIII by hydrolysis. This appears to be the first example of catalytic antibodies having a direct role in the etiology of a disease. Further characterization of these catalytic anti-FVIII antibodies may lead to the identification of novel therapeutic approaches for the future management of FVIII inhibitor patients.