Purpose: The objective of this case series is to highlight different manifestations of valacyclovir associated neurotoxicity (VAN) and demonstrate the importance of adjusting medication appropriately in patients with end-stage renal disease (ESRD) on hemodialysis to prevent these complications. Summary: Valacyclovir is a medication used to treat herpes zoster infection, commonly known as shingles. Valacyclovir is renally cleared and can accumulate in patients with renal dysfunction leading to severe side effects due to the prolonged half-life. VAN is a common adverse effect in patients with underlying kidney disease, that can be easily prevented if valacyclovir is properly dosed. This case series details the clinical outcomes of two elderly patients who were prescribed valacyclovir at six-times the recommended dose based on their renal function. Failure to reduce the dose of valacyclovir resulted in severe neurological and physical manifestations that required hospital admission and emergent hemodialysis. Conclusion: This case series details the importance of adjusting valacyclovir dose based on renal function. In patients with ESRD, the half-life of valacyclovir can be up to 14 hours, therefore hemodialysis should be utilized in severe cases of neurotoxicity to improve rapid excretion of the drug and promote rapid recovery from VAN.