Human Cytomegalovirus (HCMV) remains highly prevalent and can cause severe disease in immunocompromised hosts. Congenital infection is a leading cause of congenital neurologic defects. There is no method to eradicate latent infection from the human host, and the need for more effective therapies remains. Host telomerase has been implicated in the infection and oncogenesis of several herpesviruses. Our goal is to examine the relationship between HCMV and telomerase to identify the potential clinical and therapeutic significance. We found increased telomerase activity, and hTERT expression, following HCMV infection of human fibroblast cell lines following infection with laboratory (AD169) and clinical (TB40E) strains of HCMV. We also found sharp reduction of respective viral titers following treatment with two telomerase inhibitors of different mechanisms of action, as well as hTERT genetic knockdown, which combined suggests a biologically significant relationship between HCMV and host telomerase. Overall these findings strongly suggest telomerase is important for HCMV, and that telomerase inhibition may be a new path in the pursuit of improved HCMV therapies.