In most human gene therapy trials, the tools of gene delivery are retroviral vectors. All current vectors are derived from murine leukemia virus (MLV). Although this system is suitable for delivering a large variety of genes into different tissues, it also has its limitations and is not adequate for all potential applications of human gene therapy. Thus, attempts are underway in many laboratories to develop other gene delivery tools. Potential agents range from non-viral based gene delivery systems (eg liposomes) to other viral vectors such as those derived from adenoviruses, adeno-associated viruses, herpes simplex virus, and several other viruses. Furthermore, the development of other, non-MLV retroviral vector systems, including one derived from HIV, is in progress in several laboratories. In this article, reticuloendotheliosis viruses and their vector systems are reviewed, and their possible use in human gene therapy is discussed.