Encephalitis is an inflammation of the brain parenchyma and involves gray or white matter, or both. It may affect focal and/or diffuse and global cerebral functioning and mostly has a prodrome with influenza like symptoms. Clinical Presentation is variable and correlates with the severity of meningeal and cerebral involvement and among others, the age, comorbidities and immune status of the patient and the localization and extend of dissemination of the lesion. The etiology of encephalities can be infectious (mostly viral, but also fungal or bacterial) and immune-mediated. Symptoms may include fever, headache, myalgia, nuchal rigidity, photophobia, confusion, disturbance of consciousness, personality and behavioral changes, psychosis, new onset seizure and other focal neurological signs (e.g. aphasia and hemiparesis). Herpes simplex infection causes the most common sporadic form of encephalitis in Europe. Treatment with acyclovir can and should be started on clinical suspicion alone, as without treatment 70% of patients with HSE die.