The human enteroviruses (EV) comprise one group of the picornavirus family. The best known members are the polioviruses (PV), coxsackieviruses, and echoviruses. They replicate in the oropharynx and gastrointestinal (GI) tract and are primarily spread by fecal-hand-oral contamination. With systemic invasion nonspecific febrile illness occurs as well as specific syndromes (rashes, hand-footand-mouth disease, herpangina, pleurodynia, myocarditis/pericarditis, and conjunctivitis). With systemic replication a high level viremia may result in central nervous system (CNS) invasion. EV activity can be endemic in warm climates or epidemic in temperate climates. In temperate climates, because of improved hygiene, newborns were not exposed to EV until they were older, resulting in large epidemics of poliomyelitis, which were finally curtailed with the killed PV vaccines in the 1950s and the live oral PV vaccines in the 1960s. Today, "aseptic" meningitis is the most common neurologic syndrome caused by EV. EV are also the most common cause of viral meningitis. Other EV neurologic syndromes include encephalitis, rhombencephalitis, paralytic disease, persistent infections, and the severe group B coxsackievirus fatal systemic infections of neonates. Diagnostic clues can come from epidemics, systemic manifestations, household infections, the cerebrospinal picture, and the neurologic syndrome. However, definite diagnosis depends on laboratory methods, primarily nucleic acid amplification. Treatment of acute infections is supportive. Preventative methods include good hygiene and aggressive polio vaccination programs.