There has been an increase in systemic fungal infections over the past several decades, partially because of an increasing number of critically ill patients, surgical procedures, and immunosuppressive therapies, as well as the use of more invasive diagnostic and therapeutic medical procedures. Concomitant with this increase in infections has been the increase in azole-resistant Candida species and opportunistic molds with intrinsic resistance to many of the currently available antifungal agents. This review focuses on antifungal resistance, with emphasis on emerging resistance patterns and emerging fungi that are intrinsically resistant to antifungal agents.