Preterm premature rupture of the membranes (pPROM) is responsible for approximately one third of the over 450,000 preterm births occurring in the United States annually. In this manuscript, we summarize the outcomes and analyses related to the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network (NICHD-MFMU) network multicenter trial of antibiotics to reduce infant morbidity after pPROM. Based on evident reduction in gestational age dependent and infectious infant morbidity, we provide the rationale for aggressive intravenous and oral, broad spectrum Ampicillin/Amoxicillin, and Erythromycin therapy during conservative management of pPROM before 32 weeks' gestation. We further review the histopathologic correlates to pPROM, to antibiotic treatment, and to perinatal outcome, and discuss the relationships between maternal and neonatal cytokine levels intercellular adhesion molecule, and other clinical and plasma markers regarding perinatal morbidity. The use and limitations of ultrasound and vaginally collected amniotic fluid pulmonary maturity assessment are discussed.