Histoplasmosis is an endemic infection in most of the United States and can be found worldwide. The spectrum of this illness ranges from asymptomatic infection to severe disseminated disease. Life-threatening illness is usually associated with an immunocompromised state; however, 20 percent of severe illnesses result from a heavy inoculum in healthy persons. Culture remains the gold standard for diagnosis but requires a lengthy incubation period. Fungal staining produces quicker results than culture but is less sensitive. Testing for antigen and antibodies is rapid and sensitive when used for particular disease presentations. An advantage of antigen detection is its usefulness in monitoring disease therapy. Antifungal therapy is indicated in chronic or disseminated disease and severe, acute infection. Amphotericin B is the agent of choice in severe cases; however, patients must be monitored for nephrotoxicity and hypokalemia. Itraconazole is effective in moderate disease and is well tolerated, even with long-term use. Hepatotoxicity, the most severe adverse effect of itraconazole, is uncommon and usually transient.