Fungal infections of the central nervous system (CNS) evoke humoral and cellular immune responses with the scope to enable the host to eliminate the pathogen. Immunopathogenesis of CNS fungal infections remains incompletely understood, with most of our understanding coming from studies on experimentally infected animals. However, activation of brain resident cells combined with relative expression of immunoenhancing and immunosuppressing cytokines and chemokines may play a determinant role and partially explain immunopathogenesis of CNS fungal infections.