Significant progress has been made on the development of gene therapy for the treatment of hemophilia A, a common bleeding disorder caused by subnormal levels of blood coagulation factor VIII (FVIII). Recent advances in gene transfer technology have enabled the expression of therapeutic to physiological levels of human FVIII in normal animals as well as hemophiliac mice and dogs. However, the in vivo persistence of FVIII expression was variable, ranging from one day to over five months. Despite recent advances in the development of hemophilia A gene transfer vectors, each still faces limitations to its clinical utility. Current research is focused on improving gene transfer vehicles and delivery methods to enable sustained clotting factor expression, treatment readministration, and circumvention of the host immune response to the treatment.