Endemic mycoses remain a significant cause of morbidity and mortality among immunocompromised patients. As the number of immunosuppressed individuals increases worldwide, the incidence of endemic mycoses is also expected to rise. In immunocompromised patients, endemic mycoses can present in atypical fashion, cause more severe and/or disseminated disease, and result in higher mortality. Despite several noteworthy advances over the past decade, significant challenges remain with regard to the prevention, diagnosis and therapy of endemic mycoses in immunocompromised hosts. This review highlights important developments related to the epidemiology, diagnosis, treatment, and prevention of commonly encountered endemic mycoses. We also discuss emerging topics, knowledge gaps and areas of future research.