Idiotypic vaccination has proven successful in several animal models and human trials. Here we suggest that the expression of cross-reactive idiotypes on factor VIII (FVIII) inhibitors of patients with haemophilia A, patients with anti-FVIII autoimmune disease and natural anti-FVIII antibodies of healthy individuals, together with the ability of anti-idiotypic reagents to neutralize anti-FVIII antibodies, provides a rationale for designing a vaccine strategy aimed at preventing the occurrence of or suppressing inhibitors, based on the induction of protective anti-idiotypes. Here we discuss the rationale supporting the concept of using idiotypic vaccination to prevent the occurrence of FVIII inhibitors in patients with haemophilia A.