Abstract: Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus infections in children, and it is one of the major public health issues in China. Globally, only China has introduced monovalent inactivated vaccines against HFMD, and ideal animal models can accelerate the vaccine research and development. This article reviews recent research progress in animal models of enterovirus-associated HFMD after 2000. It discusses the advantages and limitations of each animal model and provides suggestions for the construction of animal models of enterovirus-associated HFMD, as well as the development of HFMD vaccines in China.