Scedosporium species are fungal pathogens increasingly recognized in cystic fibrosis (CF). They can cause multiresistant, life-threatening infections that are of particular concern in CF patients undergoing lung transplantation, as optimal treatment remains unclear. Here, we describe our Zurich experience of CF patients with Scedosporium infection. Disseminated infection occurred in one patient after transplantation and was successfully treated. We propose a step-by-step approach to treat candidates with colonization, and discuss our cases in the context of the current literature.