Hand Foot and Mouth Disease (HFMD) is caused by enterovirus family, in which enterovirus 71 (EV71) is the most common pathogen.Serious cases lead to neurological sympotoms and even death, especially in infants. A good EV71 infection animal model will not only help to study the mechanism of pathogenesis, and will become an effective tool for developing vaccines and treatments. Here we review advances in establishment of EV71 infection animal models in different species, and further focuse on states and prospects of EV71 infection models established by genetically modification.