Solid organ transplantation has made remarkable progress over the past three decades, evolving from a fascinating experiment in human immunobiology into the most effective means of rehabilitating patients with end-stage organ dysfunction of a variety of types. Today, at the best transplant centers, more than 90% long-term patient and allograft survival are being achieved following kidney, heart, and liver transplantation, with about 75% of lung-transplant recipients achieving these positive results. Because of these successes, the transplant community has been encouraged to ‘‘extend the envelope,’’ by bringing new forms of transplantation to the care of affected individuals. Invasive fungal infections remain a serious challenge to clinicians caring for immunocompromised patients. The proportion of vulnerable patients is increasing, paralleling the increased use of immunosuppressive therapies and the more effective supportive care in high-risk populations. Fungi responsible for these infections can be separated in two groups: the pathogenic and the opportunistic. The true pathogenic fungi cause self-limited disease in normal hosts but may cause devastating infections in compromised patients. Examples of such pathogens include Cryptococcus neoformans and the endemic fungi Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasiliensis, and Blastomyces dermatitidis. These infections may remain in a latent state only to recru- desce when the patient is immunosuppressed. Opportunistic fungi rarely cause serious disease in normal hosts but are responsible for life-threatening infection in the setting of weakened host defenses. These fungi include Candida spp. and Aspergillus spp. and less commonly Zygomycete spp., Trichosporon spp., Fusarium spp., and Pseudoallescheria boydii among others.