MicroRNAs (miRNAs) are approximately 22 nucleotide RNAs that mediate the posttranscriptional regulation of gene expression. miRNAs regulate diverse cellular processes such as development, differentiation, cell cycling, apoptosis, and immune responses. More than 400 miRNAs have been identified in humans and it is predicted that over 30% of human gene transcripts are regulated via miRNAs. Since 2004, many viral miRNAs have been described in several families of viruses. More than half of currently known viral miRNAs are encoded by viruses of the human Herepsviridae and 14 miRNAs have been found to be encoded by Human cytomegalovirus (HCMV). Thus far, HCMV is the only betaherpesvirus in which miRNAs have been described and these miRNAs possess many characteristics, including their genomic arrangement and temporal/spatial expression, which distinguish them from the other known herpesvirus miRNAs described. As a herpesvirus, HCMV establishes infection for the life of the host characterized by latent infection with periodic reactivation for production and spread of infectious progeny. This multifaceted life cycle of the herpesvirus requires an abundance of gene products and regulatory elements that makes cytomegalovirus genomes one of the most complex among human viruses. The defining characteristics of the cytomegalo virus and the minimal impact on genome size afforded by miRNAs inform the logic of virus-encoded miRNAs.