Over the past 2 decades, rare and unusual fungi, often -common soil saprophytes, have been reported increasingly as causing invasive infections in humans. Possible reasons for an increased frequency of unusual fungal infections include increasing numbers of patients with immunosuppression and increasing chance for environmental exposure. This chapter will focus on unusual and rare yeast and mould organisms and their disease manifestations. Lobomycosis, a chronic skin infection caused by the yeast-like organism Lacazia loboi, will be described, followed by infections due to basidiomycetes, and Emmonsia crescens, the agent of adiaspiromycosis. Finally, rhinosporidiosis and pythiosis will be discussed, although evidence indicates that these infections are not due to true fungi.