Maternal human immunodeficiency virus (HIV) and genital herpes simplex virus (HSV) infection in pregnancy have potential for vertical transmission that may result in death or morbidity. The risk increases with preterm delivery and prolonged ruptured membranes. When managing preterm premature rupture of membranes, the risk of transmission must be weighed against the risk of prematurity. Before 32 to 34 weeks, expectant management is preferred for patients with well controlled HIV or recurrent active genital HSV infection. For patients with advanced HIV disease or primary genital HSV infection, the risk of vertical transmission is higher and many clinical factors need to be considered.