In the past decade Enterovirus 71 (EV71) has emerged as an important cause of outbreaks of hand, foot and mouth disease in children associated with severe neurological complications. Globally, the Asia–Pacific region is the most severely affected with regular recurring outbreaks. However, endemic and sporadic cases have also been reported in other parts of the world. There is evidence that EV71 underwent rapid evolution recently, which contributed to the occurrence of outbreaks due to the lack of population herd immunity. In addition, host and environmental factors are also important. This article examines the global epidemiology of EV71 and explores the role of each of these factors.