Encephalitis is associated with significant childhood morbidity and mortality worldwide, however not much is known about the contemporary epidemiology and outcome. In this prospective multicenter pediatric encephalitis study conducted in Greece for 3 years, 42 cases were diagnosed and the presumptively or definitely causative pathogen was identified in 24 (57.1%). Leading pathogens included herpes viruses (10 patients), enteroviruses (6), and Streptococcus pneumoniae (2). No fatalities were observed; however, deficits remained in 5 of 42 (11.9%) children.