Background: Cytomegaloviruses (CMVs) have developed various sophisticated strategies to manipulate and evade the defense mechanisms of their hosts. Among the CMV genes that are predicted to be involved in these strategies are genes that encode mimics of cellular proteins, such as G protein-coupled receptors (GPCRs) and chemokines (CKs). These genes may have been pirated from the host genome during the long co-evolution of virus and host. Objectives: In this report, the putative functions of the CMV-encoded homologs of GPCRs and CKs in the pathogenesis of infection will be discussed. Study design: In order to present an overview of the current state of knowledge, the literature on the CMV-encoded homologs of GPCRs and CKs was reviewed. Results: The GPCR and CK homologs that are encoded by the CMVs represent immunomodulatory proteins with crucial roles in the pathogenesis of infection. Conclusions: In light of their function as well as accessibility on the cell surface, the CMV-encoded GPCR homologs are attractive targets for the development of new anti-viral therapies. © 2005 Elsevier B.V. All rights reserved.