Herpes simplex virus (HSV) infections are highly prevalent and may have devastating consequences if transmitted to newborns. The highest risk of transmission is when the mother has primary HSV infection (rather than recurrence of chronic infection) late in pregnancy. Clinicians should obtain a careful history, performing serologic testing and counseling as appropriate. Delayed diagnosis of neonatal HSV is associated with high mortality. Even with adequate treatment, permanent sequelae, such as cerebral palsy and developmental delay, may occur. Clinicians should develop prudent strategies to avoid primary HSV acquisition during pregnancy, and provide prophylaxis or treatment when indicated.