Herpes simplex virus (HSV) infections are fortunately quite rare in the neonatal population. Nevertheless, due to their life-threatening nature and the tremendous damage that surviving infants can incur, neonatal HSV is actually considered in a differential diagnosis relatively commonly. The availability of safe and effective antiviral therapy for the management of neonatal HSV also can accelerate a clinician's decision to consider HSV as the cause of a neonate's disease presentation, and then to obtain appropriate diagnostic studies and empirically institute antiviral treatment. Decisions on whether to continue antiviral therapy for a full course are predicated on the appropriate interpretation of these diagnostic studies as they subsequently are reported to the treating physician. For HSV-infected neonates, the duration of parenteral acyclovir therapy ranges from 14 to 21 days, depending on the extent of disease. Use of subsequent oral suppressive antiviral therapy is under investigation in randomized controlled trials, and at this time cannot be routinely recommended. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management.