First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets) in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority.