A 65-year-old lady with End-Stage Renal Failure (ESRF) receiving Continuous Ambulatory Peritoneal Dialysis (CAPD) was admitted acutely for altered mental status and neurological symptoms. She presented to the Emergency Department with bilateral upper limb weakness and clumsiness, bilateral lower limb weakness for 1 day’s duration. In addition, her family members reported altered behaviour for the previous 1 day. On examination, the patient had slurred speech, weakness in all limbs and brisk reflexes throughout. Significantly, she had been diagnosed with herpes zoster 2 days earlier by a family physician, for which she was started on oral acyclovir. Our patient was diagnosed as having acyclovir toxicity and commenced on urgent haemodialysis. Her symptoms resolved completely after 2 days. Our case details the uncommon but potentially fatal complication of acyclovir toxicity in patients with renal impairment, reinforces the importance of dose reduction in these patients and demonstrates haemodialysis as a good form of treatment for acyclovir toxicity. Family physicians should be familiar with dose adjustments for common medications prescribed to ESRF patients in the outpatient setting as the burden of chronic kidney disease increases in Singapore.