The incidence of fungal infections continues to rise as the population of immunocompromised individuals increases. Despite the enlarging numbers of infections, there are only a few antifungal agents for treatment of deep-seated, invasive infections. These agents include amphotericin B, flucytosine, terbinafine, and several azoles. Progress has been made in understanding the role of these agents in a variety of infections and this article examines in detail these agents and their prophylactic, empiric, and therapeutic uses in invasive mycoses. This article focuses on general concepts of antifungal therapies and provides a detailed review of each antifungal agent available for treatment of deep-seated mycoses.