The genes encoding the coagulation factors were characterized over two decades ago. Since then, significant progress has been made in the genetic diagnosis of the two commonest severe inherited bleeding disorders, haemophilia A and B. Experience with the genetic of inherited rare bleeding disorders and platelet disorders is less well advanced. Rare bleeding disorders are usually inherited as autosomal recessive disorders, while it is now clear that a number of the more common platelet function disorders are inherited as autosomal dominant traits. In both cases, DNA sequencing has been useful since most of these disorders are due to mutations located at the coding regions or splice sites of genes encoding the abnormal protein. However, in 5–10% of patients affected with severe clotting factor deficiencies, no genetic defect can be identified and until recently, the genetic characterization of inherited platelet disorders had been confined to the more prevalent conditions such as Glanzmann disease and Bernard–Soulier syndrome. In patients with no gene mutations identified, so far, the role of next-generation sequencing as well as of other new genomic technologies will very likely have increasing importance. However, such methods require extensive bioinformatics analysis that, in turn will require critical revision of our current diagnostic infrastructure.