Virology research and antiviral drug discovery are poised to benefit from the post-genomic revolution for three main reasons. First, viruses need the host to replicate and are therefore vulnerable to inhibition of cellular pathways. Knowledge of complete genomic sequences of both virus and host now permits the study of this interplay on a global scale. Combining transcriptomics and proteomics with large-scale gene knockdown experiments will enable the identification of novel antiviral targets. Second, massive parallel assay systems, such as DNA microarrays, which define the post-genomic era, will facilitate viral diagnostics. Third, the combination of genetics with genomics will enable the analysis of viral mutants and strains on an unprecedented scale. The dramatic effects of viral infection on host cell transcriptional patterns have been well-documented and will be briefly highlighted. In addition, we discuss recent trends that apply functional genomics methods to the discovery of new targets and therapies for viral disease.