Viruses and the immune system have been competitors throughout their co-evolution. It is therefore not surprising that the viruses in circulation today possess a variety of strategies to counteract those aspects of the immune system that are involved in virus clearance. Examination of these virus encoded functions provides an important view of immune function and an appreciation of the complexity of the virus-host interaction. It is clear that viruses, seeking to subvert the immune system, have become adept in blocking the communication channels of the immune system. There are numerous examples of viral proteins that target the cytokine networks, disrupting the processes by which the delicately balanced immune system is regulated. This review focuses on the gene products of poxviruses, adenoviruses and herpesviruses that function primarily as immune-modulators.