Gene therapy is now an established, commercially available treatment option for hemophilia A and hemophilia B. For each condition a liver-directed adeno-associated virus (AAV)-mediated gene therapy drug is available and can modify a severe phenotype to a mild one of the disease or to normalize clotting factor levels. The drugs allow stable, sustained factor expression for years with associated reduction in bleed rate and factor consumption. The most common side effect is early transient vector-induced transaminitis with a risk of losing transgene expression, requiring a period of close monitoring and possible corticosteroid treatment. However, AAV-mediated gene therapy is not feasible for many patients, including those with anti-AAV antibodies, of young age, or with liver disease, but also due to limitations set by cost or infrastructure. Alternative approaches with lentiviral vectors and gene editing are close to or in the clinical trials phase. Promising preclinical and early clinical experiences using any of these approaches have been reported for hemophilia with inhibitors, factor VII deficiency, von Willebrand disease, Glanzmann thrombasthenia, and Bernard–Soulier syndrome and will change the lives of patients soon.