Oncolytic viruses undergo multiple complex interactions with their host, meaning that many questions about their activity can only be answered in living organisms. As a result, the capacity to image viral gene expression noninvasively and repeatedly within a whole animal can significantly enhance understanding of viral activity and increases the speed of preclinical development. Similarly, imaging viral gene expression in early clinical testing creates a clearer understanding of viral tumor delivery and the level, kinetics, and biodistribution of subsequent replication. Finally, with the likelihood of imminent approval of different oncolytic viral therapies, imaging of viral gene expression would provide an early determination of therapeutic activity prior to changes in tumor burden. Here, the benefits of different reporter genes used in conjunction with oncolytic viral therapy are described, along with the imaging modalities used to measure their expression. Their applications in both preclinical and clinical testing are discussed.