BACKGROUND Acyclovir is widely used in the treatment of herpes virus infections, particularly herpes simplex virus and varicella-zoster virus. Acyclovir, when given promptly upon the start of a herpes zoster eruption, speeds healing and diminishes acute pain. OBJECTIVE Because acyclovir is a commonly used medication, it is crucial for health providers to be aware of appropriate dosing as well as possible side effects. We present this case to increase awareness of the potential for inappropriate dosing of acyclovir and the presentations of patients with toxic effects. METHODS We report the case of a 65-year-old man with a past medical history significant for chronic kidney disease who presented to the Emergency Department with progressive confusion and ataxia over 2 days. Thorough questioning in the patient's native language revealed that he had recently started a medication for a "rash." Neither he nor his family knew the name of the new medication; further investigation revealed it to be acyclovir. Although other diagnoses were considered in the differential diagnosis for this patient with altered mental status, he was treated for presumed acyclovir toxicity and given prompt dialysis, upon which his symptoms resolved. CONCLUSIONS It is important for physicians to remember that even common medications such as acyclovir can have serious side effects and complications. In this case, renal dosing was not used in a patient on hemodialysis. Acyclovir must be renally dosed and carefully monitored through drug level measurement in patients with limited kidney function to prevent serious side effects, such as the neurological sequelae demonstrated in this case report. Emergency physicians should be aware of the potential for inappropriate dosing of this medication and the presentations of patients with toxic effects.