Genital herpes simplex virus (HSV) infection has substantial economic and quality-of-life consequences; not least is the risk of transmission to the fetus/infant during parturition with the subsequent effects on the family, society as a whole and healthcare providers. While general screening programs for HSV infection are not cost effective, screening of susceptible subgroups may be acceptable in some circumstances (e.g. immunocompromised patients, presumed discordant heterosexual couples, pregnant women) despite the high costs involved. First-line options for treatment and suppression of genital herpes in Europe and the US include valaciclovir, aciclovir and famciclovir. The established efficacy of valaciclovir, along with its potential for once-daily administration in many patients (versus administration up to five times daily for aciclovir), its positive effect on quality of life, its suppressive efficacy in late pregnancy and its proven reduction of viral transmission between heterosexual discordant partners support the drug's position as a first-line therapy and suppression option in patients with genital herpes. However, the high acquisition costs compared with aciclovir will affect formulary decisions in some patients, and the favored niche for this drug, at least until evidence of prevention of transmission is demonstrated for other antivirals, would seem to be in the prevention of transmission in susceptible subgroups such as couples discordant for HSV infection (especially male-positive/female-negative couples who are planning a pregnancy), and the treatment and suppression of genital herpes in patients particularly receptive to once-daily administration.Potential disease management programs for genital herpes would thus need to balance the high costs of HSV screening and the relatively high acquisition costs of valaciclovir against the convenience of once-daily administration, the improved quality of life and the proven potential for reduced viral transmission to susceptible partners (with potential for downstream reductions in the overall socioeconomic burden of the disease) associated with oral valaciclovir.