Varicella zoster virus (VZV) is the causative agent of chickenpox and shingles. During productive infection the complete VZV proteome consisting of some 68 unique gene products is expressed through interaction of a small number of viral transcriptional activators with the general transcription apparatus of the host cell. Recent work has shown that the major viral transactivator, commonly designated the IE62 protein, interacts with the human Mediator of transcription. This interaction requires direct contact between the MED25 subunit of Mediator and the acidic N-terminal transactivation domain of IE62. A second cellular factor, host cell factor-1, has been shown to be the common element in two mechanisms of activation of the promoter driving expression of the gene encoding IE62. Finally, the ubiquitous cellular transcription factors Sp1, Sp3, and YY1 have been shown to interact with sequences near the VZV origin of DNA replication and in the case of Sp1/Sp3 to influence replication efficiency.