Every virus shares the same mission, to find a suitable host, subvert the host cells into virus-producing factories, and then spread within and to new hosts. A virus that fails at their mission is eliminated. In pursuit of their mission, viruses can be likened to spies and saboteurs. The mission requires that viruses be able to evade or override the molecular alarms, which are set off by viral structures and activities, the roadblocks and traps within the cell that are set to prevent the production of more viruses, and the innate and immune detection and weapon systems dedicated to restrict the replication and spread of these microbial spies. Viral protein synthesis is both the trigger for establishing and a prominent step in virus replication that is targeted by the major roadblocks set up by the cell to counter the viral mission. Successful viruses have developed specific molecular tools to overcome these and other host defenses. Using the espionage analogy, this review will describe the cellular and systemic protections developed by humans against virus replication and spread and the molecular tools that viruses have developed to override or evade these blocks.