Acyclovir (Zovirax) was approved for the treatment of herpesvirus infections almost two decades ago. It was the first agent in a novel group of antiviral medications that now include valacyclovir (Valtrex), penciclovir (Denavir and famciclovir (Famvir). These agents have made a dramatic impact on the morbidity associated with herpes simplex virus infections and herpes zoster. Topical and oral antiviral use have shown modest but statistically significant efficacy in treating herpes labialis with most studies demonstrating a significant reduction in episode length and/or healing time. Oral acyclovir, valacyclovir and famciclovir are efficacious and safe for the treatment of the first episode and recurrent genital herpes and are useful as suppressive therapy for individuals with frequent genital herpes recurrences. In addition, high doses of oral acyclovir, valacyclovir and famciclovir have been shown to speed the healing of herpes zoster, and data suggests that these agents also decrease associated acute and chronic pain in people of 50 years of age or older. Further research is required to clarify the safety of these agents in pregnant women with genital herpes, the role of antiviral therapy in decreasing the sexual transmission of genital herpes, and the efficacy and cost-effectiveness of these agents in treating herpes zoster in people below the age of 50 years.