Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of central nervous system caused by human polyoma virus, JC virus, which can occur in the patients with severe immune compromised condition. PML is a rare disease, seen in hematologic malignancies, organ transplantation, and HIV infected patients. PML is often fatal, because of the lack of effective anti-viral drug for JC virus. Clinical observations of survival improvement in HIV-positive patients after the introduction of combination antiretroviral therapy (cART) could suggest the importance of restoration of immune response.