In utero hematopoietic stem cell transplantation (IUHSCTx) is a promising approach for the treatment of a potentially large number of fetuses affected by congenital hematologic disorders. With technical advances in prenatal diagnosis and fetal intervention, the majority of these diseases can now be diagnosed early in gestation, allowing consideration of prenatal treatment. It, therefore, stands to reason that there is increasing interest in performing in utero hematopoietic stem cell transplantation at many centers around the world. Although the approach remains experimentally promising, expansion of clinical application will depend on improved understanding of the biological barriers to engraftment in the fetus as well as on the development of effective clinical strategies based on the hematopoietic biology of individual disorders.