Hand, Foot and Mouth Disease (HFMD) is a common childhood exanthema caused by viruses of the Enterovirus (EV) genus of the Picornaviridae family. The commonest species infecting humans is Human Enterovirus-A (HEV-A) within which group the most frequent serotypes are coxsackievirus A16 (CVA16) and enterovirus 71 (EV71). Other enteroviruses (CV-A2, -A4, -A5, -A6, -A8, -A9, -A10, -A12, -A16, -B3 and –B5) may also be associated with HFMD outbreaks, sporadic cases or asymptomatic infection. HFMD is a highly infectious disease, transmitted through direct contact with respiratory droplets, feces or blister fluid of infective patients or through contact with contaminated environments such as water, food or fomites. The clinical syndromes and severity of cases are diverse, but usually mild and self-limiting. Infants and children under 5 years old are commonly susceptible to the virus. The symptoms of HFMD include fever with blister like lesion or sores in the mouth, on hand, feet and sometimes on the buttocks. In some children with enteroviral disease, neurological complications may occur following a febrile illness but without mucocutaneous manifestations. Severe complications include encephalitis, pneumonia, myocarditis, brainstem encephalitis and acute flaccid paralysis. Epidemics of severe disease have caused great concern in SE and E Asia. High mortality and severe sequelae can be anticipated when the disease is complicated by neurogenic pulmonary edema. Children who have fever for more than three days with a temperature of 38.5°C and a history of lethargy might be at risk of neurological involvement. There are currently neither specific antiviral agents to treat nor vaccines to prevent the infection. Treating severe EV71 brainstem encephalitis patients with intravenous immunoglobulin is recommended by many experts but its efficacy is still doubtful. It is very important to establish a surveillance system to predict future outbreaks and to develop public health measures to control them. If there is an outbreak of HFMD in a school or child care center, classes with 2 or more sick children should be suspended. If there are sick children in many classes, the whole school is recommended to close for 5 to 7 days. During closure, those responsible for the school should ensure that thorough cleaning is carried out before reopening. In addition, parents are advised to ensure that their children adopt a high-standard of personal hygiene and to keep infected children at home until recovery. Copyright: ! 2012 Phommasone K and Dubot-Pérès A. This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited