Herpes simplex virus (HSV) is a sporadic viral encephalitis agent that causes high mortality and morbidity, accompanied by neurological dysfunction findings. Acyclovir is the only antiviral treatment option that should be initiated in all patients with suspected encephalitis as soon as possible. Acyclovir is rarely possible to cause allergic reactions. It may occur in a wide range from generalized cutaneous rash to Stevens-Johnson syndrome. A case of HSV-1 encephalitis who had no treatment option other than intravenous acyclovir and was successfully treated with intravenous desensitization was presented in this report. A 59-year-old male patient was admitted to the emergency department with complaints of high fever and altered consciousness. Diagnostic lumbar puncture was performed and intravenous acyclovir treatment was initiated empirically with the preliminary diagnosis of encephalitis. On the third day of the treatment, HSV type 1 polymerase chain reaction (PCR) was detected as positive. Acyclovir treatment was discontinued due to the development of a severe allergic reaction on the fifth day of acyclovir treatment. Allergic symptoms of the patient regressed with discontinuation of acyclovir treatment and application of concomitant methylprednisolone treatment. The intravenous acyclovir desensitization protocol was applied to the patient, and the patient was successfully treated. In this case, it has been shown that intravenous acyclovir desensitization can be applied in the treatment of life-threatening infections with no treatment options other than intravenous acyclovir. Our case is the first adult case in the literature to be treated with intravenous acyclovir desensitization.