Amebiasis is one of the main causes worldwide of morbidity and mortality by parasites. Application of recombinant DNA technology to the study of Entamoeba histolytica is bringing new light into our understanding of this remarkable protozoan parasite and of the disease it causes. New achievements affect the way we approach many essential questions about E. histolytica, from the mechanism of its pathogenicity to the definition of E. histolytica as a separate species from the nonpathogenic E. dispar. To give a single example, transfection of trophozoites is now possible and a new generation of studies taking advantage of this capability of manipulation is expected in the short term. Our goal with this review is to provide an updated and simple guide to the growing information on the molecular biology of E. histolytica.