In the United States, histoplasmosis is generally thought to occur mainly in the Ohio and Mississippi River Valleys, and the classic map of histoplasmosis distribution reflecting this is second nature to many U.S. physicians. With the advent of the HIV pandemic reports of patients with progressive disseminated histoplasmosis and AIDS came from regions of known endemicity, as well as from regions not thought to be endemic for histoplasmosis throughout the world. In addition, our expanding armamentarium of immunosuppressive medications and biologics has increased the diagnosis of histoplasmosis worldwide. While our knowledge of areas in which histoplasmosis is endemic has improved, it is still incomplete. Our contention is that physicians should consider histoplasmosis with the right constellations of symptoms in any febrile patient with immune suppression, regardless of geographic location or travel history.