Scedosporium prolificans infections of normal hosts usually require extensive debridement and sometimes amputation to effect cure, due to the intrinsic resistance of this species to available antifungal agents. Newer agents have not tested favourably. Variable results are obtained with voriconazole, and 100% resistance is described with echinocandins. Itraconazole and terbinafine has offered synergy against various moulds including S. prolificans. In vivo success is reported with the azole/terbinafine combination in S. apiospermum pulmonary infection and Pythium insidiosum periorbital cellulitis. We report a case of orthopaedic infection in a non-immunocompromised host with S. prolificans, in which the combinations of itraconazole/terbinafine and voriconazole/terbinafine showed synergy in vitro, and success was achieved without radical surgery, using voriconazole and terbinafine.