Varicella zoster virus infections of the central nervous system (CNS) develop preferentially in immunocompromised individuals, especially those affected by HIV and cancer. It is unclear whether treatment of herpes zoster with antiviral agents prevents the development of subsequent cerebral vasculopathy and stroke. Herpes zoster-related cerebral vasculopathy is well-documented as herpesvirus nucleocapsids have been detected by electron microscopy. Primary granulomatous angiitis of the nervous system (PACNS) is a disease in which CNS is the sole or dominant target organ of a vasculitic process, affecting the small and medium leptomeningeal and cortical arteries and, less frequently, the veins and venules. Clinical studies have reported an increased prevalence of cytomegalovirus (CMV) and herpes simplex virus (HSV) infections among individuals with accelerated atherosclerosis in the extracranial carotid arteries. In addition, histopathological studies have detected CMV and HSV particles within atherosclerotic vessels, and infection with HSV-induced atherosclerosis in avian models.