Herpes simplex virus (HSV) is regarded as a common viral pathogen that produces a wide variety of diseases. After a primary infection, which usually occurs during childhood and may or may not be clinically evident, the virus establishes a latent infection in the local sensory ganglia and can reactivate throughout the life of the individual. Fulminant hepatic failure (FHF) due to HSV infection is a clinical condition well known in pediatric, immunocompromised, and pregnant patients. It is rare in immunocompetent hosts. We report the case of a 51-year-old man with no significant past medical history who developed FHF with disseminated intravascular coagulopathy and septic shock secondary to HSV infection. The initial diagnosis was made through a frozen section of a needle liver biopsy and the presence of HSV was confirmed in the permanent section with immunohistochemistry. HSV was grown in cell culture from liver tissue obtained through an autopsy.