Fungal infections cause substantial morbidity and mortality, particularly in immunocompromised patients. Current antifungal agents are not adequate to control these infections. The fungal pathogen, Cryptococcus neoformans causes fatal meningioencephalitis with over one million new cases every year resulting in 600,000 deaths, mostly in sub-saharan Africa. An attractive target for antifungal agents is the cell wall, since the cell wall is an essential organelle and the cell wall biosynthetic enzymes are absent in humans. Our laboratory is identifying novel targets for antifungal agents and is focusing in three main areas. The first is biosynthesis of chitin-related polysaccharides in the wall, including chitosan, the deacetylated form of chitin. The second is resistance to oxidative and nitrosative stresses that Cryptococcus encounters and successfully overcomes inside phagocytic cells. The third is signal transduction pathways that lead to remodeling of the cell wall and resistance to oxidative and nitrosative stress.