The incidence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections may be broken into two broad categories: opportunistic and endemic. The most important agents of the opportunistic mycoses are Candida spp., Cryptococcus neoformans, Pneumocystis jirovecii, and Aspergillus spp. (although the list of potential pathogens is ever expanding); while the most commonly encountered endemic mycoses are due to Histoplasma capsulatum, Coccidioides immitis/posadasii, and Blastomyces dermatitidis. This review discusses the epidemiologic profiles of these invasive mycoses in North America, as well as risk factors for infection, and the pathogens' antifungal susceptibility.