Many viruses asymptomatically co-exist within the human host. Understanding the mechanisms by which these viruses persist—in the absence of overt disease—is the major focus of our lab. These stealthy viruses are also powerful tools for probing and understanding cell biology important to signaling, immune evasion, cell survival, and differentiation. Human cytomegalovirus (CMV) is a beta-herpesviruses that persists in the majority of the world’s population by establishing a latent infection. Latency is defined as a reversibly quiescent state during which viral gene expression and replication is highly restricted. We use CMV as a model for defining and understanding the interactions between viruses and their hosts that allow for the entry into and exit from latent states. Understanding latency and viral persistence is critical to developing novel antiviral therapies to control persistence and its consequences in at-risk individuals, such as stem cell and organ transplant recipients.