Invasive fungal infections have evolved into significant causes of morbidity and mortality in premature infants, immunocompromised children, and patients receiving immunosuppressive agents. Since the discovery in 1955, amphotericin B has been the cornerstone of antifungal treatment. The past 10 years, however, have witnessed a major expansion in the antifungal armamentarium through the development of less toxic formulations of Amphotericin B, the introduction of improved triazoles, and the advent of the echinocandin lipopeptides. In this article we discuss the Lipid-based amphotericin B, Voriconazole (a new azole), and Caspofungin (an echinocandin).