Abstract: Hand, foot and mouth disease (HFMD) is a common contagious disease in children under 5 years old, and caused by a variety of different enterovirus infection. There were several large-scale outbreaks of the disease in China and other Asia-Pacific region. The first inactive EV71 vaccine was approved in China in December 2015. The univalent vaccine prevents a part of the epidemics. However, there is no multivalent vaccines for HFMD. This article reviews the progresses in the development of multivalent HFMD vaccines as well as animal models.