In the early twentieth century, Tobacco mosaic virus (TMV) was both an economic problem for tobacco, pepper and tomato growers, and an experimental model system for plant pathologists and virologists. It became the right tool for the job in the first big push to understand the nature of a virus, in particular its constituent chemical components: RNA and coat protein that formed the virus particle. This work, as elaborated by Creager, reveals the intimate links between basic and applied biology and how TMV became a model system for virology, biochemistry, and structural biology between 1935-1960. Today, TMV continues as the right tool and has accumulated several 'firsts'. These include the use of its coat protein trans-gene to mediate protection from subsequent infection by related TMV strains, the biology and mechanism of how TMV spreads from cell to cell using the 30-kilodalton (kDa) movement protein, and the cloning of the TMV N gene from TMV-resistant tobacco followed by the identification of the novel features of the first cloned resistance genes [3-6].