Viruses have long been used as model organisms for molecular processes and as tools for finding critical cellular regulatory proteins and pathways, as well as pathogenesis and disease. The development of proteomic approaches, combined with recent advances in mass spectrometry methods, has greatly aided the detection of virion components, protein interactions in infected cells, and virally induced changes in the cellular proteome, resulting in a much more detailed understanding of viral infection. Furthermore, the growing amount of high-resolution structures for viral proteins has benefited in the discovery and understanding of specific inhibitors that could be utilized in antiviral treatments, as well as providing important information on the mechanisms of action of these proteins.