Blastomycosis is the least understood of the major endemic mycoses in North America. The fungus exists in the soil in its mycelial form, and when the proper growth conditions exist growth and spore formation will occur. When microfici containing the growing mycelium of blastomyces are disturbed, an infecting aerosol is formed. The spores are inhaled and eventually settle in the alveoli where multiplication by binary fission occurs. Following development of cell-mediated immunity the infection is localized in the lung. During the pre-immune phase of the infection spread to extrapulmonary sites may occur. Most common sites of involvement include the skin, bones, prostate and central nervous system. Pulmonary disease may resolve spontaneously or progress. Treatment is required for progressive pulmonary illness and all episodes of extrapulmonary disease. For life-threatening blastomycosis or blastomycosis of the central nervous system amphotericin B is the treatment of choice, while ketoconazole is an excellent alternative for patients who are not critically ill or have no central nervous system involvement.