Human herpesviruses have coevolved with humans over millions of years, and adaptation of latent infection within the cells of the immune system is a unique characteristic of many of these viruses. Following primary infection, these herpesviruses establish an asymptomatic-persistent infection in healthy individuals that is strictly controlled by virus-specific CD8(+) and CD4(+) T cells. Here, we provide a brief overview of how the human immune system interacts with these latent viruses and regulates the lifelong host-virus relationship in healthy virus carriers. Extensive studies on T-cell-mediated immune regulation over the last decade has allowed researchers to successfully translate these findings into the clinical setting to treat various herpesvirus-associated diseases in transplant patients and individuals with virus-associated malignancies. It is highly likely that these newly emerging T-cell-based therapeutic and diagnostic technologies will revolutionize the clinical management of patients with herpesvirus-associated diseases.