Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical “awakening” to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths.