Herpes simplex virus (HSV) infections are ubiquitous. Children are infected with HSV resulting in totally asymptomatic acquisition to life-threatening disease. Therapy of HSV diseases of children can be considered according to severity and time of acquisition. Neonatal herpes simplex virus infections take one of three forms--disease localized to skin, eye, or mouth (SEM), encephalitis, or multiorgan disseminated disease. Treatment consists of intravenous (IV) administration of acyclovir. Supportive care for patients with life-threatening disease is an integral component of patient management. Mucocutaneous HSV infections in the immunocompromised host can be treated with either intravenous acyclovir or one of the orally bioavailable antiviral therapies. For hospitalized patients, therapy consists of IV acyclovir at 5 mg/kg every 8 hours for 7 to 14 days. For ambulatory patients, therapy is tailored according to age. For children less than 12 years of age, oral acyclovir is administered at a dosage of 20 mg/kg every eight hours. Although no controlled studies have been performed with valaciclovir or famciclovir, the pharmacokinetics of these medications would suggest superiority over acyclovir. Dosage recommendations have not been established for young children. For postpubertal children, dosage should mirror that of adults. Valaciclovir is administered at 500 mg twice daily. Famciclovir is administered at 125 mg three times daily. Herpes simplex keratoconjunctivitis is treated with topical triflurothymidine. Two drops are applied to the infected eye five times daily until resolved. Recurrences are managed in a similar manner. Some physicians administer oral acyclovir at the doses noted above in order to prevent frequent recurrences. Genital HSV infections can be treated with acyclovir, valaciclovir, or famciclovir. Episodic treatment of recurrent episodes is usually not necessary in childhood. Importantly, all data on the use of these compounds for these conditions have been generated in adults. Physician judgment is required for the management of recurrent herpes labialis, erythema multiforme, and herpes gladitorum. No controlled studies have been performed in children, although experience with acyclovir, valaciclovir, and famciclovir have resulted in their use.