Herpes simplex virus is the most common cause of severe and potentially fatal sporadic encephalitis worldwide. Recurrence of neurologic symptoms after resolution of the initial episode of HSV encephalitis and despite adequate treatment with intravenous acyclovir is well recognized albeit rare. Most of these recurrences had no evidence of replicating virus and are immune in nature with only a minority of these recurrences representing true virologic relapses. Immunocompromised patients are predominantly at greater risk for virologic relapse of HSV encephalitis with potentially severe and at times fatal consequences. We describe a patient with small cell lung cancer and brain metastasis who underwent chemotherapy, treatment with dexamethasone and whole brain radiotherapy who subsequently suffered two episodes of HSV encephalitis three months and seven months after completion of radiotherapy and while on dexamethasone treatment.