Herpesviruses, particularly human cytomegalovirus and Epstein-Barr virus, play a key role in periapical lesions that are symptomatic. Indeed, periapical lesions may be stable and asymptomatic until they become symptomatic, which could be caused by the activation of latent herpesviruses within the lesion. Given the risk of serious systemic complications from herpesvirus infection, the dentist's early detection and treatment options for periapical lesions may have a positive impact on a patient's overall health, particularly in immunocompromised patients. The present treatment techniques for periapical lesions of endodontic origin need to be updated to incorporate the contributions and possible morbidity caused by herpesvirus infection