Gastrointestinal histoplasmosis (GIH) is an uncommon disease with protean manifestations. It may occur as a result of mediastinal histoplasmosis or in the setting of progressive dissemination. GIH may be misdiagnosed as inflammatory bowel disease, malignancy, or other intestinal diseases leading to inappropriate therapies and unnecessary surgical interventions. Patients with bowel obstruction, perforation, or bleeding, and systemic findings suggestive of histoplasmosis should be evaluated for GIH. This is especially true for immunosuppressed patients, especially those with AIDS. Diagnosis first requires consideration of histoplasmosis in the differential in patients with the above types of gastrointestinal abnormalities, and second, familiarity with a battery of mycologic and serologic tests. Progressive disseminated histoplasmosis (PDH) is lethal if left untreated, and treatment is highly effective. This review will focus on the clinical and histopathologic features of GIH, the approach to diagnosis, and recommendations for treatment.