Anti-fungal agents are classified under two major headings, systematic and topical agents. Only systematic anti-fungal agents will be discussed in this chapter. Since the discovery in 1955, amphotericin B has been the cornerstone of anti-fungal treatment. It is active against most species of fungi. However, Candida lusitaniae, Pseudallescheria boydii, and fusarium spp have primary resistance to amphotericin B. Recently, new liposomal preparations of amphotericin B have been developed. They are less nephrotoxic. The azole family of anti-fungal includes two broad classes: the imidazoles (clotrimazote, ketoconazote, miconazole) and the triazoles (flucouazole and itracouazole). Imidazoles are still widely used for the treatment of superficial mycoses and vaginal candidiasis. The systematic triazoles are more slowly metabolized and have less effect on human synthesis than imidazoles, hence they are preferred for systemic therapy. Flucytosine is a fluorinated pyrimidine. Clinically, the principal use of flucytosine is as adjunctive therapy with amphotericin B in the treatment of candidial or cryptococcal diseases, Griseofuluin is derived from penicillium. It is fungistatic in vitro for species of dermatophytes. It is useful for the treatment of tinea capitis and tinea unginum.