Human parechoviruses (HPeVs) are single-stranded, positive-sense RNA viruses and are classified in the genus Parechovirus of the family Picornaviridae. Echovirus 22 and 23 were reclassified as HPeV1 and 2 in 1999. Although HPeVs were considered to be one of the common viruses which cause mild gastroenteritis and respiratory infections, the concept of HPeVs has changed significantly after the discovery of HPeV3 in 2004. HPeV3 infection is an emerging infectious disease which attracts the attention of pediatricians, because it can cause sepsis and meningoencephalitis in neonates and infants younger than 3 months, which could lead to neurological sequelae and death. In Japan, the epidemics of HPeV3 infection have occurred every 2 or 3 years since 2006 and we had an epidemic in 2014 summer. Fever, severe tachycardia, poor activity and appetite are typical symptoms of HPeV3 infection.In addition, abdominal distention, umbilical protrusion, palmar-plantar erythema,and mottled skin are occasionally observed in patients with HPeV3 infection. Currently diagnosis is usually made by PCR using serum and/or cerebrospinal fluid. The reason why severe disease occur only in neonates and young infants remain unknown; however, negative or low maternally derived neutralizing antibody titers to HPeV3 are suggested to be a risk factor for developing severe HPeV3-related diseases in neonates and young infants. So far, no specific antiviral therapy is available, thus supportive care is the only option. It is likely that epidemics of HPeV3 continue to occur given there are children with absence or lack of neutralizing antibodies against HPeV3. The research related to HPeV3 pathogenesis, specific therapy, and prevention are definitely warranted.