Cytomegaloviruses (CMVs) are species-specific beta-herpesviruses whose replicative success is largely due to establishment of novel mechanisms for altering the host immune response. CMV encodes 3 families of putative G-protein coupled receptors (GPCRs) likely pirated from the host cell. While the functions of these virally encoded GPCRs remain unclear, the receptors possess potent signaling abilities. Understanding the molecular regulation of these GPCRs will provide important insight into CMV pathogenesis.