Enterovirus-D68 (EV-D68) is a unique enterovirus, similar to human rhinoviruses, spread via the respiratory route and primarily causing respiratory disease. Increasing clusters of EV-D68 associated respiratory disease have been reported since 2008, with the largest reported outbreak occurring in North America in 2014. Epidemiologic data and biological plausibility support an association of EV-D68 with the neurologic condition, acute flaccid myelitis. Diagnosis requires EV-D68 specific PCR or viral sequencing of respiratory specimens. Treatment consists of supportive care, as there are no currently available effective vaccines or antiviral therapies. Further research is needed to prepare for future EV-D68 outbreaks of respiratory or neurologic disease.