Herpes simplex virus (HSV) infections are a significant cause of morbidity among immunocompromised patients, and in some instances these infections may be a primary cause of death. The overwhelming majority of these infections are caused by reactivation of the virus. The natural history of reactivated HSV infections in immunocompromised patients has been well described, and these infections occur predictably in particular patient populations. Antiviral therapy has been shown to be effective in treating or preventing HSV infections. Randomized, controlled, double-blind studies have demonstrated that acyclovir is the most effective compound currently available for treatment or prevention of HSV infections.