Important progress has been achieved in antifungal chemotherapy in recent years. Two groups of drugs are now used: those produced by various organisms and those made synthetically. In the first group, only amphotericin B (1956) administered systemically is active in numerous deep mycoses. Although toxicity limits the use of amphotericin B, it is still the drug of choice for systemic mycoses. Griseofulvin was the first agent used for oral treatment of dermatophytoses. The introduction of flucytosine began a new era in chemotherapy; however, although flucytosine is orally administered and rapidly distributed, its antifungal activity is limited to cryptococcosis and systemic candidosis. The rapid induction of flucytosine-resistant mutants led to the development of treatment regimens of amphotericin B plus flucytosine. With the development of imidazole derivatives in 1969, a new generation of azole antifungal agents has emerged. Of these, only ketoconazole was orally active. New azole derivatives and triazoles have been synthesized, but only itraconazole has been successful in the treatment of superficial and deep mycoses in humans. Future trends for the development of agents with fungicidal activity, wider spectra, and better distribution are proposed. The association of immunotherapy with antifungal chemotherapy may offer new treatments for fungal infections in immunocompromised patients.