An increased understanding of the molecular mechanisms of cancer and the ability to introduce exogenous genes into mammalian cells has led to the development of oncologic treatment strategies based upon gene transfer. Preclinical animal models have suggested a variety of approaches which are now being tested in pediatric trials. Studies using marker genes to trace cell origin have already generated important information regarding autologous bone marrow transplantation for pediatric cancers. A variety of therapeutic genes are also being clinically tested. Trials are underway to determine if introduction of immunostimulatory genes into cancer cells can be used to enhance host antitumor immunity. Treatment of primary brain tumors with insertion of drug sensitization genes is a promising new therapy that is also being clinically evaluated. Other strategies such as insertion of drug resistance genes into hematopoietic cells, anti-oncogene therapy, and tumor suppressor gene replacement are being tested in adults and may find use in pediatric cancer treatment. Although gene transfer offers promising new approaches for the therapy of pediatric cancer, many technical problems remain which limit efficacy and widespread use. Further basic research in the molecular biology of cancer and in vector development will be required to realize the full potential of gene therapy strategies.