Entamoeba histolytica (a protist parasite that infects humans) has a rather simple, actin-based cytoskeleton. Cytoskeleton dynamics are important markers of pathogenicity, as expressed by the invasion of human tissues, phagocytosis of epithelial cells and activation of the host’s immune response. As the cell’s major actin-binding proteins, myosins are hallmarks of these pathogenic activities. Here, we review myosins in the light of recent, genomics-based approaches.