This chapter focuses on the epidemiological risks from mixed virus infections and transgenic plants expressing viral genes. Several types of interaction may occur between a virus infecting a transgenic plant and either the transgene transcript or its translation product. These include heterologous encapsidation or interaction with a transmission accessory factor, which have the potential to alter vector specificity; complementation from a protein involved in cell-to-cell or long-distance movement, with possible effects on tissue tropism or the ability to establish a systemic infection; synergism resulting in increased replication and/or increased symptom severity; and recombination resulting in gain of function or alteration of pathogenicity. The chapter reviews the general aspects of vector specificity in different virus groups, as this could be altered either by recombination or by virus–transgene interactions. Potential complementation in a transgenic plant would also be limited in epidemiological effect, as the complementing transgene would not be present in nontransgenic plants. The chapter also discusses various means of minimizing the perceived risks of interactions between viruses and transgenically expressed viral sequences and the potential benefits to be gained from virus-resistant transgenic plants in comparison to the perceived risks.