Cryptococcus neoformans is an encapsulated yeast mainly responsible for meningoencephalitis, especially in AIDS patients. Recent observations using an experimental model of systemic cryptococcosis that mimics the human infection have reinforced the knowledge on the pathogenesis of cryptococcosis. Cryptococcosis may occur several years after inhalation of infecting particles from the environment. A stage of fungemia that reflects the dissemination of infection usually precedes the development of meningoencephalitis. The capsule mainly composed of glucuronoxylomannan constitutes the main virulence factor of C. neoformans. It has several deleterious effects including the inhibition of the host immune responses. The central nervous system involvement differs between AIDS patients and HIV-negative patients. In AIDS patients, histological studies of the brain show numerous cryptococci without significant inflammatory cell response. In other immunodepressed hosts, a granulomatous inflammation containing few yeasts is usually seen. This may reflect an altered local immunological defect against C. neoformans in AIDS patients with cryptococcosis.