Fungal osteomyelitis and joint infections are uncommon diseases that very present unique treatment challenges in comparison to bacterial infections. The number of antifungal agents has been greatly enriched by new discoveries such as second generation triazoles and echinocandins. Voriconazole is a second generation triazole antifungal agent currently approved for the treatment of aspergillosis, candidiasis, and infections caused by scedosporium apiospermum and fusarium spp. The aim of this chapter is to discuss the rationale for the use of voriconazole in orthopaedics for the treatment of fungal osteomyelitis and periprosthetic infections. Current treatment recommendations combine systemic antifungal therapy and surgery including debridement, abscesses or joint drainage, and removal of prosthetic implants. Voriconazole has been reported to be active against infections caused by candida spp., aspergillus spp., fusarium spp. and scedosporium spp., whereas few reports have demonstrated efficacy in histoplasmosis, coccidioidomycosis, and blastomycosis. Recent studies have reported the successful use of voriconazole in antifungal impregnated cement spacers for the two stage revision of periprosthetic infections.