Blastomycosis is an endemic fungal infection predominantly seen in the south central and mid-western United States and portions of Canada. The disorder is caused by Blastomyces dermatitidis, a dimorphic organism usually acquired through inhalation of aerosolized conidia. Most acutely infected patients are asymptomatic or develop a self-limited respiratory illness. Chronic pneumonia is the dominant clinical manifestation of blastomycosis, although extrapulmonary disease is common, usually involving skin and subcutaneous tissue, bones and joints, the prostate gland, and the central nervous system (CNS). Chronic blastomycosis should always be treated with systemic antifungal therapy, and oral itraconazole is the drug of choice for mild to moderate forms of the disease. Severe manifestations, including adult respiratory distress syndrome, CNS involvement, and disease in severely immunocompromised hosts require primary therapy with an amphotericin B formulation. There are no routine measures to prevent blastomycosis, although there is promising experimental data involving the use of a live, attenuated vaccine.