Understanding the effects of viral infection has typically focused on specific virus-host interactions such as tissue tropism, immune responses and histopathology. However, modeling viral pathogenesis requires information about the functions of gene products from both virus and host, and how these products interact. Recent developments in the functional annotation of genomes using Gene Ontology (GO) and in modeling functional interactions among gene products, together with an increased interest in systems biology, provide an excellent opportunity to generate global interaction models for viral infection. Here, we review how the GO is being used to model viral pathogenesis, with a focus on animal viruses.