Herpes simplex encephalitis is a common viral encephalitis associated with significant morbidity and mortality if not diagnosed and treated early. Neurosurgery may be an impetus for viral reactivation, either from direct nerve manipulation or high-dose steroids often administered during cases. The authors present the 40th known case of herpes simplex virus (HSV) encephalitis following neurosurgical intervention and review the previously reported cases. In their review, the authors observed positive HSV polymerase chain reaction (PCR), which had initially been negative in several cases. In cases in which there is high suspicion of HSV, it may be prudent to continue antiviral therapy and retest CSF for HSV PCR. Antiviral therapy significantly reduces mortality associated with HSV encephalitis.