Genital herpes is a sexually transmitted disease that has been widely investigated from both an epidemiological and a diagnostic viewpoint. Better knowledge of the disease has pointed to the important role of asymptomatic herpes simplex virus type 2 shedding as a major culprit for the spread of the virus in the world, the latest statistics showing that the incidence of genital herpes is constantly increasing. The reference compound for the treatment and prophylaxis of genital herpes is acyclovir. Recently, two drugs with better oral bioavailability, valaciclovir, the oral prodrug of acyclovir, and famciclovir, the oral prodrug of penciclovir, have been made available. Nevertheless, there is a need to develop additional approaches, to extend the therapeutic possibilities and to face the problem of emerging resistant viruses, mostly in immunocompromised patients. Therefore, efforts have been made in different directions including the exploration of new targets for antiviral chemotherapy, the use of immunomodulators and the development of specific vaccines.