Less common and emerging fungal pathogens are often resistant to conventional antifungal therapy and may cause severe morbidity and mortality in immunocompromised hosts. Some Scedosporium species may be completely resistant to antifungal therapy. Hyaline septated filamentous fungi, such as Fusarium species, Acremonium species, Paecilomyces species, and Trichoderma species, are increasingly reported as causing invasive mycoses refractory to amphotericin B therapy. Dematiaceous septated filamentous fungi, such as Bipolaris species may cause pneumonia, sinusitis, and CNS infections that are unresponsive to current medical interventions. Trichosporon spp are resistant to the fungicidal effects of amphotericin B. An increasing number of different members of the class Zygomycetes are reported as causing lethal infections, despite aggressive medical and surgical interventions. Infections due to these and other less common and emergent fungal pathogens will likely continue to develop in the settings of selective anti-fungal pressure, permissive environmental conditions, and an expanding population of immunocompromised hosts.