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Neonatal herpes simplex virus infection is often severe, if not fatal. What is our understanding of the epidemiology of this disease? How is it diagnosed? Would maternal screening for herpes simplex virus-2 (HSV-2) in pregnancy make a difference? Does maternal HSV alter transmission of HIV vertically or horizontally or both? These questions continue to be pursued and unfortunately, there are few clear answers.A nationally reportable incidence and case definition of neonatal herpes simplex virus is desirable but not yet in effect. Maternal screening for HSV during pregnancy is becoming prevalent but not supported by any national committee or recommendation. Several lines of research have demonstrated HSV expression facilitates HIV transmission. Recently, HSV suppression has been attempted to decrease horizontal transmission of HIV.Neonatal herpes simplex virus infection is a rare and serious neonatal illness. The true burden of disease is uncertain. Several recent retrospectively determined incidences identify a case rate of about one per eight thousand live births. HSV reactivation occurs more often than previously thought. Current prophylactic HSV strategies do not decrease horizontal or vertical transmission of HIV-1.