Fungal pathogens are an increasingly recognized complication of organ transplantation and the ever more potent chemotherapeutic regimens for childhood malignancies. This article provides a brief overview of the current state of systemic antifungal therapy. Currently licensed drugs, including amphotericin B and its lipid derivates; 5-fluorocytosine; the azoles, including fluconazole, itra-conazole, and voriconazole; and a representative of the new class of echinocandin agents, caspofungin, are discussed. Newer second-generation azoles (posaconazole and ravuconazole) and echino-candins (micafungin and anidulafungin) that are likely to be licensed in the United States in the next few years also are addressed.