For the last ten years, non-Aspergillus mold species have been increasingly involved in human invasive infections, probably as a consequence of more intense immunosuppression and prolonged patient survival, and of selective pressure since antifungal agents are currently used for prophylaxis or therapy. Scedosporium prolificans, one of these emerging fungi, has been isolated in a broad spectrum of clinical presentations in humans, including respiratory-tract colonization, superficial or locally invasive infections, and disseminated infections in immunocompromised patients. Here, we report the recent emergence of invasive infections due to S. prolificans in France, and describe four new cases diagnosed during the last six years. Only one disseminated scedosporiosis has been reported before this in France, in 1994. Three out of our four cases were breakthrough infections in immunocompromised patients receiving posaconazole or voriconazole therapy. The aims of the present review were thus to gain a better understanding of scedosporiosis epidemiology and clinical features, and to review recent advances in multimodal management of these infections, including surgery, recovery and/or enhancement of immunity, and antifungal combinations, especially voriconazole plus terbinafine.