A 35-yr-old, immunocompetent male was admitted complaining of severe odynophagia. He was diagnosed as having herpes simplex esophagitis and was started on intravenous acyclovir 5 mg/kg every 8 h on the day of admission. His response was dramatic. Within 24 h he was virtually asymptomatic. Acyclovir therapy in immunocompetent adults with esophagitis has been described in only a handful of cases in the literature, although the therapy is well established in immunocompromised patients. We review the English literature and discuss the efficacy of the therapy. Acyclovir therapy may be beneficial in immunocompetent patients with particularly severe odynophagia.