Cryptococcus neoformans, a human pathogenic fungus, infects immunocompromised humans and causes serious diseases such as cerebral meningitis. C. neoformans controls the expression of virulence factors in response to the host environment via various signal transduction pathways. Understanding the molecular mechanisms involved in C. neoformans infection will contribute to the development of methods to prevent and treat C. neoformans-related diseases. C. neoformans produces virulence factors, such as a polysaccharide capsule and melanin, to escape host immunity. Several proteins of C. neoformans are reported to regulate production of the virulence factors. In this review, on the basis of studies using gene-deficient mutants of C. neoformans and animal infection models, we outline the signal transduction pathways involved in the regulation of virulence factors.