Histoplasma capsulatum is the most common endemic mycosis worldwide. Although most of the globe's largest urban hubs fall outside this organism's regions of endemicity, clinicians practicing in a metropolis like New York City or Los Angeles must nevertheless remain vigilant for histoplasmosis because of the large immigrant population that is served by its hospitals. H. capsulatum infection ranges from asymptomatic pulmonary infection to life-threatening diffuse pneumonia with dissemination. The early years of the AIDS epidemic first introduced U.S. clinicians working in areas previously unfamiliar with histoplasmosis to newly immunocompromised patients from endemic regions presenting with disseminated H. capsulatum originally acquired in their home countries. Improvement in HIV prevention and therapeutics has reduced the frequency of such cases. Herein we report three cases of histoplasmosis encountered in our New York City institution over the last three years to emphasize that awareness of this infection remains mandatory for the frontline urban clinician.