More prevalent than initially considered, histoplasmosis is primarily a non-contagious disease of the reticuloendothelial system, producing a broad spectrum of clinical manifestations, ranging from asymptomatic or self-limited infection, in immunocompetent patients to life-threatening, disseminated disease in immunocompromised ones. The causative agent is H. capsulatum, a thermally dimorphic, intracellular fungus, discovered in 1906, by the pathologist Samuel Darling, when examined tissues from a young man whose death was mistakenly attributed to miliary tuberculosis. Since then, histoplasmosis was described on six continents, with high and low endemicity areas. H. capsulatum is a soil-based fungus, commonly associated with river valleys in the temperate zone, and with the presence of bird and bat guano. Infection occurs when saprophytic spores are inhaled and change to the pathogenic yeast in the lungs, where H. capsulatum overcomes many obstacles to cause host injuries. Depending on geographic distribution, morphology, and clinical symptoms, three varieties have been historically recognized, two of them (var. capsulatum and var. duboisii) being pathogen to humans, and the third (var. farciminosum) has predominantly been described as an equine pathogen. In endemic areas, patients with AIDS or people who receive immunosuppressive therapies should be counseled to avoid high-risk activities; otherwise, precautionary measures should be taken.