Studies have demonstrated the benefit of acyclovir, given intravenously or orally, on the acute illness in herpes zoster (HZ). Whether or not such treatment influences the subsequent development of postherpetic neuralgia (PHN) has been the subject of recent controversy. Intravenous acyclovir has not been shown to influence PHN significantly in prospective studies. Oral acyclovir in large doses may reduce PHN during the 3 months after acute HZ, but this effect has not been observed consistently in well-designed studies. From 3 months onwards, no trial has demonstrated a significant effect of oral acyclovir in reducing PHN. The way forward is discussed.