The goal of gene therapy for bleeding disorders is to provide stable insertion and expression of a particular gene whose absence is responsible for a particular disease. The bleeding disorders for which the most basic and clinical research has been completed are the hemophilias factor VIII deficiency and factor IX deficiency. These X-linked diseases are caused by single-gene mutations; replacement of the defective gene has not only resulted in clinical and biochemical improvement in animal models but also provided promising results in phase I clinical trials. An ideal gene transfer approach to the treatment of hemophilia would require a minimally invasive procedure for gene delivery, have minimal associated morbidity, and result in long-term transgene expression, ideally yielding factor levels in the therapeutic range. Multiple approaches to gene transfer in the hemophilias are currently under investigation.