Invasive mycoses pose a major diagnostic and therapeutic challenge. Advances in antifungal agents and diagnostic methods offer the potential for improved outcomes in patients with these infections, which are often lethal. Many fungal pathogens occur almost exclusively in opportunistic settings--in the immunocompromised host--and these infections are the focus of this review. Several areas of ongoing challenge remain, including the emergence of resistant organisms and the absence of reliable markers for early identification of patients at risk of developing invasive fungal disease. This Seminar reviews the changing epidemiology of invasive mycoses, new diagnostic methods, and recent therapeutic options and current management strategies for these opportunistic pathogens.