Histoplasmosis is the most common endemic mycosis causing human infection. Large outbreaks have been ascribed to histoplasmosis, but most infections are sporadic. Similar to the other fungi in this category, initial exposure to Histoplasma capsulatum is by way of the respiratory tract, but once inhaled into the alveoli, the organism readily spreads in macrophages throughout the reticuloendothelial system. Compared with a decade ago, improvements in diagnostic tests have made it feasible to more quickly establish a diagnosis of histoplasmosis, thus allowing appropriate antifungal therapy to be started promptly. Treatment guidelines have been updated recently and are reviewed for the various forms of histoplasmosis.