Neurological disease is the initial manifestation of acquired immunodeficiency syndrome (AIDS) in 10-20% of patients with HIV infection. Progressive multifocal leukoencephalopathy (PML) predominantly involves the cerebral hemispheres, with a small subset of patients having lesions predominantly or exclusively confined to the cerebellum. The radiological features of PML are typically non-inflammatory. As a result of potent antiretroviral therapy (ART), however, inflammatory lesions are becoming more common in HIV-infected individuals and are due, in part, to immune reconstitution that occurs in recipients of potent ART. In the majority of such cases, the clinical outcome of immune reconstitution PML has been beneficial to the host, although several case reports have described worsening or fatal outcomes in PML patients as a result of potent ART. The following 2 cases of immune reconstitution PML described in this report illustrate the varied radiological manifestations and clinical outcomes that can develop in AIDS patients with PML receiving potent ART. Moreover, these cases highlight the inflammatory changes observed on neuroimaging in AIDS patients with immune reconstitution PML receiving potent ART and to our knowledge are the first reports of immune reconstitution isolated to the cerebellum in such patients.