Molecular diagnosis of gene defects that cause the various phenotypes of inherited deficiencies of coagulation factors depends on the mapping and cloning of the respective genes and the analysis of mutations that cause these phenotypes. Direct and indirect molecular diagnoses (using DNA polymorphisms) are the methods currently used for the most common coagulation disorders. Haemophilia A is due to defects on the X-linked gene of factor 8. The most common mutation in patients with severe haemophilia A is a partial inversion of factor 8 mediated by a 9.5 kb sequence, present in the large intron 22 of factor VIII and twice more about 400 kb telomeric to it. Studies of more than 2000 patients with severe haemophilia A showed that different types of the partial inversion account for 43% of the molecular defects in those patients. Almost all mothers of these patients are carriers of the inversion and the majority of these inversions occur in male germ cells. This inversion could be easily diagnosed by Southern blot analysis. Besides the common inversion, a large number of different molecular defects have been found in patients with haemophilia A. As a rule, each unrelated family shows a private molecular lesion. Missense mutations are the predominant defects in patients with mild-to-moderate disease (≈ 87%). Large deletions account for about 5% of patients, while frameshifts due to small deletion/insertions and nonsense codons are found in 46% of patients with severe disease. The current methodology to detect these defects is laborious and not suitable for a routine hospital laboratory. Therefore, the majority of these defects are diagnosed indirectly using DNA polymorphisms to mark the abnormal gene in a given family. The development of “DNA-chips” for hemophilia A would likely provide a solution to the problem of direct detection of these mutations. The molecular diagnostic approaches for factor 9 deficiency(haemophilia B), von Willebrand disease and recent progress in the understanding of the pathophysiology of these disorders using transgenic mice and the study of potential regulatory molecules will be presented.