In agriculture, virus diseases have traditionally been controlled by deploying genes for resistance, and when resistance genes are inaccessible, physical and chemical controls have been used. The latter include removing weeds that serve as reservoirs for viruses and insects that vector the viruses, and the use of chemical insecticides to control the insect vectors. (aphids, whiteflies, plant hoppers, etc. With the advent of gene transfer technologies, genes for disease resistance have been introduced to crops either individually or in combinations with other useful genes. Genes for resistance have come from resistant plants [e.g., the ‘N’ gene for resistance to tobacco mosaic virus (TMV)] and from the pathogen, applying a strategy referred to as “pathogen-derived resistance” (PDR). Using PDR, resistance has been developed via genes that encode viral RNAs but not proteins (applying RNA-based gene silencing) and genes that encode viral proteins (coat proteins and replicase proteins are most common). Examples of crops in which PDR has been used in commercial agriculture include potato (for resistance to potato leaf roll virus, potato virus Y), papaya (papaya ringspot virus), squash, melon, and other cucurbits (cucumber mosaic virus, multiple potyviruses). A variety of other crops are in various stages of development. Research has been ongoing to determine the cellular, molecular, and structural mechanisms of resistance. We developed mutants of the coat protein (CP) of TMV that are incapable of assembly, thereby eliminating concerns of non-specific trans-encapsidation of RNA, yet provide superior degrees of resistance. Some of the CPs blocks virus disassembly only, while others block disassembly plus virus replication and local spread of infection. Studies in other groups are in progress to determine the basis of resistance that is conferred by expression of genes encoding viral replicases and other proteins. Many such studies also include experiments that address certain biosafety concerns that have been raised by scientists and/or environmental groups, such as the likelihood of RNA-recombination, insect acquisition and transmission, and impacts on resistance in potential outcrossing species. These and related studies will support the validity of using certain genes, but (perhaps) not others, in transgenic crops to develop virus resistance.