Diseases caused by the parasite Entamoeba histolytica disproportionately affect residents of underdeveloped areas, afflicting places lacking sufficient sanitation, hygiene, and water processing especially. While the recent differentiation between Entamoeba histolytica and the morphologically identical but completely asymptomatic Entamoeba dispar based on genetic and biochemical analyses has enhanced the study of the disease-causing parasite, a mystery still exists as to the factors which still cause about 90% of Entamoeba histolytica infections to remain asymptomatic after colonization. Researchers delving into these areas have identified several features of the parasite—including the galactose and N-acetylgalactosamine inhibitable adherence lectin, proteinases, and amoebapores, all virulence factors in Entamoeba—and of the host, including the association of anti-lectin IgA with resistance to disease, which may determine whether infection is invasive. As specific and easy diagnostics are developed to aid in identifying more precisely the health burden caused by E. histolytica, vaccine candidates are under evaluation.