Progressive multifocal leukoencephalopathy (PML) is a fatal neurodegenerative disease characterized by subacute CNS demyelination caused by the reactivation of the dormant human polyomavirus, JC virus (named after James Cunningham, the patient from whom the virus was first isolated). JC virus is considered ubiquitous, with ~70% of healthy individuals possessing JC virus antibodies; these antibodies are thought to remain dormant in the bone marrow or kidneys and get activated at the time of immunosuppression. Though only 1–4% of patients with HIV have PML, usually presenting with CD4 counts below 200 cells/𝜇L, ~80% of those with PML also have HIV. Additionally, those on immunosuppressive therapy, or with hematological malignancies or autoimmune diseases are at a higher risk of developing PML.