Modern biotechnology has significant potential to increase agricultural productivity to meet the demand for food from an increasing world population. Transformation of plants with viral genes has been proven in many cases to produce resistance to the virus from which the genes were derived. The technology has been successfully used to produce resistance in agriculturally important crops such as papaya, potato, tomato, squash, wheat and others. The benefits of transgenic virus resistance include increased yield, reduced pesticide use to control the vectors of viruses, and improved crop and food quality. The coat protein (CP) gene is most often used to confer resistance. In some cases, the expression of CP correlated with resistance, and strong evidence for prevention of uncoating was shown. For some viruses there can be both CP and RNA mechanisms that can confer resistance in transgenic plants. High levels of resistance can be produced in plants transformed with a viral replicase gene, which includes the full-length gene as well as various deletions or sequence modifications. The mechanism of resistance in replicase-expressing plants is complex and may involve expression of a protein that blocks virus replication and/or movement, as well as post-transcriptional gene silencing. In general, it has been demonstrated that plants resistant to mechanical inoculation are also resistant to vector transmission. The development of transformation techniques broadens the possibility of use of engineered virus resistance in plant breeding. There are many destructive virus diseases of crop plants worldwide, and biotechnology may be the fastest and most efficient way to produce resistant cultivars. One example of this is production of transgenic papaya in Hawaii that showed field resistance to a potyvirus, specifically papaya ringspot virus (PRSV). However, Hawaiian resistant papaya did not confer resistance to Asian isolates of PRSV. To address the problem of PRSV impact on Asian papaya production, the Papaya Biotechnology Network was formed and is sponsored by five Southeast Asian (SE Asian) countries (Malaysia, Thailand, Philippines, Vietnam and Indonesia) and by the International Service for the Acquisition of Agri-biotech Application, with technical and financial support from Monsanto. A comprehensive plan was developed for genetic enhancement of papaya and subsequent technology transfer to SE Asia. The CP and replicase (NIb) genes from the most common PRSV isolates from four participating countries were cloned and sequenced. The sequences revealed a high degree of PRSV divergence in SE Asia that implicates the need for using genes from local strains in generation of resistant transgenic papaya. Several binary vectors for Agrobacterium-mediated transformation were constructed, using both CP and replicase genes and their modifications. A large effort is currently being undertaken in Network laboratories to adopt Agrobacterium transformation systems of papaya. Transgenic plants are now being produced and will soon be tested for PRSV resistance. Strategies for resistant line selection, agronomy tests, assays for regulatory approvals, and finally breeding and commercialization are under development. Prior to commercialization, extensive field testing and regulatory approvals are required to address agronomic performance, preservation of cultivar characteristics, and food/environmental safety. If successful, the technology would improve the yield and quality of papaya fruit in SE Asia.