The IE86 protein of human cytomegalovirus (HCMV) is unique among viral and cellular proteins because it negatively autoregulates its own expression, activates the viral early and late promoters, and both activates and inhibits cellular promoters. It promotes cell cycle progression from Go/G1 to G1/S and arrests cell cycle progression at the G1/S interface or at G2/M. The IE86 protein is essential because it creates a cellular environment favorable for viral replication. The multiple functions of the IE86 protein during the replication of HCMV are reviewed.