Enterovirus type 71 (EV71) (Picornaviridae family, Enterovirus genus, HEV-A species) belongs to the most neuropathogenic non-polio human enteroviruses. CNS damages caused by EV71 in children were very similar in their clinical and pathomorphological pattern and frequently indistinguishable from those induced by virulent strains of poliomyelitis virus. During the past 30-40 years, EV71 has caused large outbreaks of hand, foot, and mouth disease (HFMD) in the countries of Europe (Bulgaria, Hungary) and Southeastern Asia (Malaysia, Taiwan, Singapore, China and others). HFMD (rash on the hand and foot skin and oral mucosa) affects children aged 1 month to 12-14 years, mostly with favorable outcomes in 3-7 days. On 2-5 days of HFMD, ≈ 1% of less than 2-3-year-old children were found to have neurological syndromes, such serous meningitis, poliomyelitis-like signs (pareses and paralyses of the extremities), brainstem encephalitis (tremor, myoclonic jerks, lethargy, bulbar palsy, acute heart and pulmonary failure, neurogenic pulmonary edema, shock, coma, death). In severe cases, mortality rates were as high as 92-94%. Motor, respiratory, and psychoemotional disorders remained long in a small portion of the patients. Pathomorphologic studies revealed damages to the neurons located in the respiratory and cardiovascular centers of the reticular formation of the medulla oblongata, to the nuclei in the n. vagus, and to the anterior nuclei of the spinal cord. The changes in myocardial and lung tissues were minor or absent. The main causes of pulmonary edema were damages to the nerve centers of the brainstem brain and dysregulation of the autonomic nervous system. Drugs and vaccines against EV71 infection are currently unavailable. Immediate (during the first days of EV71 infection) hospitalization of children with the earliest prognostic signs (temperature 38.5-39°C within ≥ 3 days, lethargy) of CNS involvement, early intravenous administration of human immunoglobulin, and active cardiovascular therapy (administration of milrinone) are recommended to reduce the incidence of severe and fatal cases of EV71 infections.