HSV-1 and HSV-2 infect approximately two-thirds of the world's population regardless of sex, geography, or climate. The ubiquitous nature of this infection is due to lifelong host infection, asymptomatic infection of the oral or genital mucosa, and low morbidity and mortality. Close person-to-person oral or genital contact is necessary for HSV transmission because the virus enters through mucous membranes or epidermis.

Primary VZV infection causes chickenpox in children, a common disease before the vaccine became widely available in 1995. Because humans are the only reservoir of this highly contagious airborne virus, the incidence of chickenpox has declined since the vaccine became available.

Viruses are a common cause of encephalitis, with a variety of factors influencing the epidemiology, clinical presentation, and management of the disease. Host immune status is a key factor in herpesvirus infection of the central nervous system. This section focuses on CMV, EBV, and HHV6, which can cause encephalitis in the setting of organ transplantation and immunosuppression.

As more and more patients are receiving immunosuppressive therapy, human herpesvirus infections are becoming more common. Historically, human herpesvirus infections were described as temporal lobe encephalitis caused by herpes simplex virus type 1 or type 2. However, more recently, other pathogens, such as varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6, have been identified as causing severe neurological infections.