The prognosis of HIV-related disorders have markedly improved after highly active antiretroviral therapy was introduced, however, following initiation of the therapy, some patients with severe immunodeficiency develop a paradoxical clinical deterioration despite decreased HIV viral load and increased CD4+ T-cell counts. These phenomena are recently recognized as immune reconstitution inflammatory syndrome (IRIS). It is considered that the rapid restoration of the immune system leads to exuberant inflammatory responses to antigenic stimuli. Although the disorders are sometimes life-threatening, the definition and the management of IRIS have not been established yet. We review the current knowledge of IRIS, especially in the area of HIV-related CNS disorders. Cryptococcal meningitis and progressive multifocal leukoencephalopathy (PML) are common disorders which cause CNS IRIS. HIV encephalopathy is also reported to develope IRIS. Infiltration of cytotoxic CD8+ T lymphocytes is observed in the suffered brain tissue of PML and HIV encephalopathy, and it may be one of the pathogenic factors.