Cryptococcus neoformans is a basidiomycete that can cause life-threatening meningoencephalitis in patients with and without impaired immune function. Cryptococcosis is usually an opportunistic infection in patients with compromised immunity as a consequence of HIV-1 infection, steroid administration, cancer chemotherapy, sarcoidosis, diabetes, or inherited immune system defects. This pathogenic yeast has a defined sexual cycle, which allows classical genetic analysis. Molecular biology approaches, including transformation and gene disruption by homologous recombination, and animal models for studies of virulence are both well developed. Recently an international consortium convened to begin the C. neoformans genome sequencing project, and we review here background and arguments for this project. We also discuss the importance of this project to the biology and virulence of this organism in particular, and to virulence in general.