Acyclovir is an antiviral medication often used to treat outbreaks of herpes in children. Acyclovir has an exceptional safety profile; there is a possibility that it might induce severe nephrotoxicity in rare cases. In this report, we present the case of a 17-year-old girl with acute renal injury as a side effect of using acyclovir. The patient was admitted for three days due to drug-induced AKI, which was reversed by discontinuing the afflicted medicine (acyclovir), initiating appropriate hydration with intravenous normal saline 0.9%, and refraining from any nephrotoxic medications. Following up a week later, the patient was asymptomatic and had normal kidney function. Therefore, it is critical to use acyclovir correctly to avoid possibly fatal consequences.