Scedosporium species are now increasingly isolated from immunocompromised and immunocompetent patients. Unfortunately, Scedosporium species infections are generally resistant to amphotericin B, and S. prolificans strains are particularly resistant to presently-available antifungal agents. Here we review the microbiology, expanding epidemiology, numerous clinical presentations, and diagnostic tools available for Scedosporium species infections. Finally, we detail the available in vitro, animal model, and clinical data on the treatment of Scedosporium species infections with special emphasis on the role of newer antifungal therapies for these recalcitrant infections.