Cryptococcus neoformans is a major fungal pathogen of both humans and animals. The fungus can be divided into two varieties, with each variety being composed of two serotypes. A sexual phase has been identified, which classifies C. neoformans as a bipolar heterothallic fungus with two mating types, MATa and MATalpha. The analysis of mating and mating type in this organism is important for a number of reasons. Both clinical and environmental isolates display a severe bias of the MATalpha mating type over MATa. MATalpha cells are also more virulent than MATalpha cells. Molecular and genetic analyses of the genes that make up the mating pathway have revealed that some of these genes are required for virulence. Finally, although it is well known that infection begins in the lungs after inhalation of infectious particles, it still remains unclear what constitutes the infectious particle. This review will discuss current information about what is known about the role that mating type and morphology play in virulence.