Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. A battery of diagnostic studies including serology, antigen, cytology/histopathology, and culture should be obtained in suspected cases of histoplasmosis. The yield of antigenuria detection is highest when the multiple body fluids are tested; the level of antigenuria correlates with severity of disease. Amphotericin B is the treatment of choice for severe pulmonary or disseminated histoplasmosis, and itraconazole is effective for mild to moderately severe infection. Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures.