Herpes simplex virus 1 (HSV-1) is a nearly ubiquitous human pathogen, remaining dormant in its human host the majority of the time. The interaction between HSV-1 and the immune system represents a complicated balance of power that allows the virus to persist in the host for a lifetime. However, disruptions in the immune system can activate the virus with the potential to cause devastating infections in the central nervous system (CNS). We present a patient who suffered three consecutive yearly HSV-1 CNS episodes (encephalitis, seizure, and retinitis), each within days of his influenza vaccination. We highlight subtle immunologic defects in this patient that may have allowed unchecked viral replication and resultant disease manifestations, as well as the potential role of influenza vaccine in tipping this balance in favor of HSV-1.