This article presents a history of Entamoeba histolytica spanning since the remote times when it was not even recognized as a cause of human disease to the recent molecular advances. Feder Losch (1875) in Saint Petersburg, found amoebae in fecal samples but only regarded them as responsible for maintaining the inflammatory process, not as a cause of dysentery. Fritz Schaudinn (1903) established the differentiation between Entamoeba histolytica and Endamoeba coli, Schaudinn decided to call it E. histolytica because of its ability to cause tissue lysis. Emile Brumpt (1925) based on experimental studies, pointed out the existence of E. Histolytica as a species complex, comprising two morphologically indistinguishable species, E. dysenteríae which is the cause of symptomatic infection, and Entamoeba dispar found only in asymptomatic carriers. Louis Diamond et al (1961) during the 1960s developed an axenic culture medium for E. histolytica which allowed in vivo and in vitro studies. Sargeaunt and Williams (1978) distinguished for the first time E. histolytica strains by isoenzyme electrophoresis, thus confirming that E. hystolytica was indeed a species complex comprising both pathogenic and non-pathogenic species. William Petri et al (1987 demonstrated that the 170 kDa protein with greater antigenicity was the Gal/GalNac-specific lectin. Diamond and Clark (1993) described again Brumpt's original 1925 hypothesis, concluding that there was enough evidence to support the existence of two morphologically indistinguishable species, a pathogenic and a nonpathogenic one, corresponding to E. histolytica and Entamoeba dispar respectively. The World Health Organization accepted this hypothesis in 1997.