Scedosporium apiospermum, the asexual anamorph of the cosmopolitan fungus Pseudallescheria boydii, is emerging as an important cause of disseminated infection in immunocompromised patients. We present our experience with the first reported case of S apiospermum fungemia in a lung transplant patient. Disseminated infection resulted in sepsis, multiorgan failure, and death. Review of the literature highlights the diagnostic difficulties related to the similarities between S apiospermum and Aspergillus sp. This superficial resemblance has a significant impact on clinical outcomes considering the inherent resistance of Scedosporium to amphotericin B, the traditional antifungal of choice for disseminated hyalohyphomycoses.