Primitive hematopoietic progenitor and stem cells have been pursued as highly desirable targets for genetic therapy. Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells; however, both preclinical and early clinical studies indicate that the gene transfer efficiency of the current generation of vectors using known transduction conditions into primate and human repopulating stem cells is too low to be of clinical utility in most situations. In this presentation I will summarize the status of our completed and ongoing clinical genetic marking trials, and describe our efforts in the laboratory and use of primate transplantation models to improve on these results.