One of the many applications of gene transfer for cancer gene therapy is the transfer of drug-resistance genes into bone-marrow stem cells for myeloprotection. Protection of the hosts' bone marrow should allow for dose escalation that may be useful for eradicating minimal residual disease in a post-transplant situation. A number of drug resistance genes, whose products include mutant forms of enzymes that confer resistance to chemotherapeutic drugs, are discussed. Advances in hematopoietic stem cell isolation and ex vivo manipulation has kept pace with improvements in retroviral vector technology to make hematopoietic stem cell transduction a distinct reality. Clinical trials, which have established that the approach is safe, are now being designed to address more therapeutically relevant issues.