Impairment of cell-mediated immunity is the chief predisposing condition for the development of PML. Lymphoproliferative disorders, either chronic lymphocytic leukemia or lymphoma, were the underlying immunosuppressive conditions in Astrom, Mancall, and Richardson’ s initial characterization of PML as a distinct clinical entity in 1958. Through the beginning of the AIDS epidemic in 1981, lymphoproliferative disorders remained the most common predisposing illness for PML. In a review of 230 cases of PML published in 1984 by Brooks and Walker, PML wasseeninassociationwithlymphoproliferativediseases in 62.2% of the cases (Brooks and Walker, 1984). Other predisposing illnesses included myeloproliferative diseases in 6.5%, carcinoma in 2.2%, granulomatous and ine ammatory diseases, such as, tuberculosis and sarcoidosis, in 7.4%, and other immune dee ciencystatesin 16.1%. Although AIDS was included in the latter category, there were only 2 reported cases of PML complicating AIDS at that time (Brooks and Walker, 1984), the e rst of which was reported in 1982, only 1 year after the seminal description of AIDS. Until the AIDS pandemic, PML remained a rare disease. Indeed, for most practicing neurologists, it remained a medical curiosity that was seldom observedinpractice. Following theAIDSpandemic, the incidence of PML changed very dramatically. In major metropolitan areas, the disease can hardly be regarded as rare. By the late 1980s, AIDS was reported to be the most common underlying disorder predisposing to the development of PML at institutions in New York(Krupp etal, 1985)and Miami(Berger etal, 1987). Gillespie and colleagues (Gillespie et al, 1991) studying the prevalence of AIDS-related illnesses in