Abstract: Scedosporium species are ubiquitous opportunists capable of a wide spectrum of disease. In patients with cystic fibrosis (CF), colonization and, rarely, infection have been reported. We discuss a novel case of disseminated Scedosporium apiospermum in a CF patient presenting as multifocal osteomyelitis of the thoracic spine and left hand that was successfully treated with long-term voriconazole who was successfully treated with long-term voriconazole. We review the epidemiology, microbiology, diagnosis, treatment, and prognosis of scedosporiosis focusing on the CF and lung transplant populations. Tissue diagnosis with molecular techniques and drug sensitivity testing should be used in cases of suspected scedosporiosis due to high frequency of drug resistance. Timely initiation of and prolonged therapy with voriconazole are associated with improved clinical and radiographic outcome. Pre–lung transplant colonization with Scedosporium predisposes to disseminated infection with high morbidity and mortality in the posttransplant period. Optimal peri-transplant management of the CF patient with pre-transplant Scedosporium colonization or infection remains unknown and should be prioritized in research agendas.