This study included all 18 cases of children hospitalized for encephalitis in the referral university hospital of Heraklion, Crete, Greece, during the 5-year period from 2000 to 2004. Encephalitis was attributed to viral infection (echovirus, herpes simplex virus 1, varicella-zoster virus, cytomegalovirus, and influenza A) in eight children and to bacteria (Mycoplasma pneumoniae, group A beta-hemolytic streptococcus, and Rickettsia typhi) in a further five cases. Multiple hyperintense brain lesions on magnetic resonance imaging (MRI) were associated with a severe clinical presentation but not with a guarded long-term outcome. Five children still presented with mild to moderate sequelae after 1.5 to 5.3 (median 4.0) years. Our findings confirm the elimination of measles, mumps, and rubella-associated encephalitis in the postvaccine era. MRI appeared to be of great diagnostic value. Although no fatalities were observed, deficits did persist in several patients.