Viruses replicate inside host cells, where they use host biochemical and structural components to facilitate the production of new virus particles. As a consequence of co-evolution with their hosts, viruses have acquired host genes and genetic mutations that confer dominance over normal cell function. Research on virus–cell interactions has focused on the identification of mechanisms of virus dominance in order to develop therapeutic strategies for preventing productive infection. Although such research remains an essential part of molecular virology, viruses are also important genetic tools that can be used to analyse cell function. Because virus genomes contain genetic information, some of which was derived from host cells, it is possible that the analyses of virus–host interactions might lead to the identification of functionally dominant virus genes and novel eukaryotic counterparts. In this article, we have described how transforming and non-transforming viruses can control cell motility (cell migration or membrane projection), and explained how the analysis of virus cytopathic effects (CPEs) led to the identification of a novel family of cellular genes that regulate diverse aspects of cell motility.