The diagnosis of histoplasmosis depends on recognition of the different clinical manifestations of infection, accompanied by knowledge of the accuracy and limitations of tests used for diagnosis of fungal infections. Although most infections are asymptomatic, histoplasmosis can be severe, or even fatal, in patients who have experienced a heavy exposure, have underlying immune defects, or develop progressive disease that is not recognized and treated. This article provides an up-to-date clinical review of histoplasmosis, focusing on recognition, diagnosis, and management.