Melanins can be produced by some species of pathogenic bacteria, helminths and fungi. The production of melanin appears to contribute to microbial pathogenesis owing to its potential for protection against host defence systems. Melanin synthesis in Cryptococcus neoformans has been associated with virulence by the ability to protect against phagocytosis, oxidative injury and phagocytic killing. Moreover, it was shown that, melanization of C.neoformans has involved in protection against some antifungal compounds. The detection of the association between melanin and microbial virulence might provide new treatment and prevention strategies targeting the inhibition of melanin polymerization. In this review article, the impact of melanin on virulence of C.neoformans has been discussed.