Amphotericin B remains an important choice for central nervous system (CNS) fungal infections, although its adverse effects have limited its use, especially nephratoxicity. New formulations of amphotericin B, new azoles and echinocandins have been developed for clinical use in the past decade. However, high mortality is associated with CNS fungal infections, especially those due to filamentous fungi. Mortality risk of cerebral mucormycosis approaches 100% although amphotericin B and neurosurgical intervention are used. Use of voriconazole has improved prognosis of cerebral aspergillosis. However, the mortality risk of the disease remains 70%. The antifungal therapy of minimum of CNS fungal infections due to yeast fungi and endemic fungi, such as Candida spp. Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis has been standardized. However, high mortality and increase of CNS fungal infections resistant to standard therapy is waiting for utility of new antifungal options. The treatment of CNS fungal infections due to less common and newly emerging fungi, such as Acremonium species, Fusarium species, Pacilomyces species, Trichoderma species, Trichosporon species, Zygomycetes, and Phaeohyphomectes is challenging and no well-designed studies have been carried out, the available data are based on case reports. In conclusion, the prognosis of CNS fungal infections is not good. Early diagnosis, appropriate use of antifungal agents and management of underlying disease, in combination with neurosurgical intervention may improve the outcome.