Histoplasmosis occurs throughout the world but is more common within the endemic areas of North America, particularly in fertile river valleys. Disease manifestations range from asymptomatic infection in the normal host with low-inoculum exposure to rapidly fatal, disseminated infection in the severely immunocompromised host, emphasizing the importance of cellular immunity in defense against Histoplasma capsulatum. Diagnosis depends on a high index of suspicion, knowledge of the clinical and epidemiologic features of the infection, and a thorough understanding of the uses and limitations of fungal cultural and serological laboratory procedures. Recently, a method has been developed for rapid diagnosis based on detection of a polysaccharide antigen in body fluids of patients with histoplasmosis. Amphotericin B remains the preferred treatment for more severe forms of histoplasmosis, particularly in the immunocompromised host, but oral treatment with ketoconazole or newer imidozoles appears to be effective in less severe infections in non-immunocompromised individuals.