In terms of improving the quality of life of patients with recurrent genital herpes simplex infection, suppressive antiviral therapy is an effective strategy. Acyclovir is the treatment of choice for herpes simplex virus (HSV) infections. In an Indian study it was stated that acyclovir was not being prescribed because of the high price of the drug. Continuous-dose therapy is more effective than episodic therapy in suppressing recurrences. Although there were not any records to show acyclovir is either teratogenic or mutagenic in humanbeings, it should be known that any agent interferes with DNA syntesis must be used with caution during pregnancy. Transplacental passage of acyclovir has been documented. Recently there are several reports on successful therapy of acyclovir-resistant HSV with oral zidovudine and IV trisodium phosphonoformate (foscarnet) which is a drug under research and active against human immunodeficiency virus (HIV) and cytomegalovirus. Bid valacyclovir is as effective and well tolerated in the treatment of recurrent genital herpes infection as 5-times-daily acyclovir. Therefore, valacyclovir could be an useful alternative to acyclovir. Valacyclovir twice-daily was found as effective and safe as acyclovir five-times-daily in the treatment of recurrent genital herpes infection. In the treatment of the first clinical episode of genital herpes infection, recommendations of the Center for Disease Control and Prevention (CDC) are as follows: oral acyclovir 400 mg, 3 times a day or oral acyclovir 200 mg, 5 times a day; or oral famciclovir 250 mg, 3 times a day; or oral valacyclovir 1 g, bid, each for a duration of 7–10 days. Currently, antiviral therapy including acyclovir and more recently famciclovir and valacyclovir are the mainstays of the treatment of HSV disease in humans. A group of physicians has used cimetidine to prevent recurrent HSV infections. Since the 1930s a research was underwent to find out a form primary prevention of herpes genitalis or an immunotherapy for the established disease. The vaccines first preparated as inactivated whole virus preperations, by the time they became advanced technologically to include virion components or subunits, replication impaired HSV mutants, nonpathogenic replicating vectors, and plasmids expressing one or more HSV genes. Recombinant DNA vaccine and mutant HSV type 2 vaccine researchs were performed. DNA vaccine was proved to be immunogenic in mice, rats, guinea pigs and baboons. The vaccine has prevented recurrences in animals infected with HSV type 2. On the other hand the vaccine has provided prophylaxis in uninfected animals when challenged with HSV. Human testing of the vaccine is underway. Imiquimod (R-837), an immune response modifier, can be effectively used to treat primary genital HSV disease and can suppress HSV infection recurrences in the guinea-pig. Some similar immune response modifiers may play role in the treatment of genital warts but just imiquimod was currently approved by Food and Drug Administration (FDA). For the entire 15 weeks of observation period, imiquimod alone reduced recurrence rate by 62.6%, while addition of HSV vaccine to imiquimod reduced recurrence rate by 80.6% compared to placebo/placebo. Resiquimod, also known as R-848 or S-28,463, is a member of the imidazoquinoline that is a family of immune response modifiers. Resiquimod is a more potent analogue of imiquimod. Imiquimod was approved in the United States as a 5% cream formulation (Aldera) for the treatment of external genital warts. In animal From the Department of Dermatology, Trakya University, Medicla Faculty, Edirne, Turkey; Dermatology Unit, Kaplan Medical Center, Rechovot, Israel; and the Department of Dermatology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. Address correspondence to Binnur Tuzun, MD, Trakya University, Medical Faculty, 22030, Edirne, Turkey. E-mail address: yalcintuzun@superonline.com