Combination antifungal therapy has been an area of great research and clinical interest since antifungals became available decades ago, in part driven by the severe morbidity and mortality associated with invasive fungal infections. Because of the availability of newer antifungal agents including echinocandins and expanded-spectrum triazoles, interest in combination antifungal therapy for invasive mold disease, especially invasive aspergillosis, has grown. This review examines combination antifungal therapy for the treatment of yeast and molds, including current studies evaluating combination antifungal therapy in three clinically important invasive fungal infections: candidiasis, cryptococcosis, and aspergillosis. This article focuses on recent clinical data and potential future clinical directions. Copyright © 2007 by Current Medicine Group LLC.