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Cryptococcosis is a severe fungal disease causing 220,000 cases of cryptococcal meningitis yearly. The etiological agents of cryptococcosis are taxonomically grouped into at least two species complexes belonging to the genus Cryptococcus. All of these yeasts are environmentally ubiquitous fungi (often found in soil, leaves and decaying wood, tree hollows, and associated with bird feces especially pigeon guano). Infection in a range of animals including humans begins following inhalation of spores or aerosolized yeasts. Recent advances provide fundamental insights into the factors from both the pathogen and its hosts which influence pathogenesis and disease. The complex interactions leading to disease in mammalian hosts have also updated from the availability of better genomic tools and datasets. In this review, we discuss recent genetic research on Cryptococcus , covering the epidemiology, ecology, and evolution of Cryptococcus pathogenic species. We also discuss the insights into the host immune response obtained from the latest genetic modified host models as well as insights from monogenic disorders in humans. Finally we highlight outstanding questions that can be answered in the near future using bioinformatics and genomic tools. [ABSTRACT FROM AUTHOR]