Postherpetic neuralgia (PHN) is a painful condition occurring after herpes zoster (shingles) in which pain persists in the area where the rash emerged. Treatments for PHN are either partially, or totally, ineffective for many people with PHN. Attention has therefore turned to approaches that may prevent the development of PHN. Antiviral agents, used at the time of the rash, are the best-established preventative approach. To investigate the effectiveness of antiviral agents in preventing PHN from developing, we conducted a systematic review. We identified six trials involving 1211 participants, that were suitable for inclusion in the review. There was no significant difference between the antiviral (either oral acyclovir or oral famciclovir) and placebo control groups in the presence of PHN four or six months after the rash onset. Oral acyclovir was ineffective in reducing the incidence of PHN, while insufficient evidence was found to recommend other antiviral treatments to prevent PHN. Further well-designed, randomised, controlled trials of famciclovir or other new antiviral agents with a greater number of participants are needed. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different groups of people, such as people who are immunocompromised.