Frequently, diseases caused by black yeasts are chronic in nature with a high morbidity. In addition, these infections are often fatal and relapse is common, even after prolonged treatment. Although the CLSI Document M38-A outlines methods for antifungal susceptibility testing of moulds, Exophiala spp. are not directly discussed. In an effort to determine the antifungal susceptibility patterns of Exophiala spp. we tested 160 clinical isolates against amphotericin B, itraconazole, posaconazole, and voriconazole in a head-to-head comparison. Posaconazole and itraconazole were the most active in vitro with MICs falling well below the achievable serum levels typically observed with standard dosing regimens.