For many years virulence of pathogenic Entamoeba histolytica has been attributed to the capacity of the parasite to destroy tissues through the expression and/or secretion of various molecules. Such view is supported mainly by in vitro experimentation, whereas data obtained by using animal models of the disease have clearly demonstrated that the host's inflammatory response is primarily responsible for tissue damage. This review analyzes the content and/or activity of some of the presumed toxic amebic molecules present in amebic strains with different degrees of virulence compared to various parasite in vitro functions that are supposed to correlate with in vivo virulence. The analysis suggests that amebic virulence is primarily determined by the parasite's capacity to adapt and survive the aerobic conditions present in animal tissues. This initial episode in the host-parasite relationship is an absolute requirement for the further development of tissue lesions, which result from the concerted action of many molecules derived from both, the host and the parasite.