Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, was first recognized as a dermotrophic virus that usually cause mild, self-limiting hand-foot-and-mouth disease (HFMD). However, EV71 infection can sometimes induce a variety of severe neurological complications and even death. Current large outbreaks of EV71 make this virus being a major public health issue. Intense effort has been made to address its underlying pathogenesis and to develop effective means for combating EV71 infections. Here, we aimed to provide an overview of cellular mechanisms underlying EV71 infection and to assess potential agents for prevention and treatment of EV71 infections.