The mechanisms by which Entamoeba histolytica trophozoites adhere to and lyse target cells are reviewed from the perspective of pathogenesis. Adherence via the galactose and N-acetyl-galactosamine inhibitable amebic lectin and possible additional amebic adhesin molecules is followed by target cell death. Inhibition of the Gal/GalNAc lectin with GalNAc inhibits amebic cytolysis of target cells. Amebic activities implicated in the cytolytic event include vesicle exocytosis and maintenance of an acid pH, pore forming proteins, phospholipase A and proteases. Increased knowledge of the sequence of events leading to target cell lysis should lead to more effective treatment or prevention of infection by this enteric parasite and add to our basic understanding of eukaryotic cell-cell interactions.