Histoplasmosis is an important systemic mycosis in the Americas, Asia, and Africa. Increasingly cases are recognised in nonendemic areas. Proper management requires recognition of the clinical syndromes caused by Histoplasma capsulatum infection, familiarity with the uses and limitations of the diagnostic tests, an understanding of the indications for treatment and role of specific antifungal agents. This review will address these issues with the goal of providing physicians in non-endemic areas sufficient information to suspect, diagnose, and treat patients with histoplasmosis.