Herpes simplex encephalitis, which is caused by herpes simplex virus type 1 and type 2, is a severe central nervous system infection. This disease starts with fever, convulsion, and impaired consciousness, and often accompanies with temporal robe symptoms such as hallucination, cognitive disturbance. In spite of the establishments of early diagnosis by polymerase chain reaction (PCR) and effective antiviral therapies, the prognosis of herpes simplex encephalitis is still poor and often accompanies neurological deficits. New treatment strategy including combination therapy should be developed to ameliorate the prognosis of the disease.