Preterm premature rupture of membranes (PPROM) occurs in 3% of all pregnancies and is responsible for approximately one-third of all preterm births, causing significant perinatal morbidity and fetal death. In a significant number of PPROM cases an infection is present although it is sometimes difficult to determine clinically. Our knowledge of pathophysiology of intrauterine infection/inflammation and impact of antibiotic therapy on its clinical course is elementary. It is known that intrauterine infection/inflammation is a significant risk factor for developing neurological impairment in children. Prophylactic administration of antibiotics might eradicate infection in women with PPROM and improve neonatal outcomes, on the other hand, it could only increase the period of latency and suppress infection to a subclinical level without eradicating the underlying infection, leaving the fetus in an unfavorable intrauterine environment. Still, the European and the American guidelines recommend routine administration of antibiotic therapy in women presenting with PPROM. Studies have shown that administration of antibiotics increases the period of latency and improves certain short-term neurological outcomes such as reducing the rate of abnormal cerebral ultrasound scan prior to the discharge from hospital, but it does not reduce perinatal mortality, the rate of preterm births and does not have an effect on long-term neurological outcomes. Furthermore, guidelines for antibiotics administration on PPROM are largely based on deficient, low quality and possibly outdated evidence. Optimal regimen and duration of antibiotic therapy are not clear and new studies estimating changes in bacterial resistance and more common clinical use of cephalosporines in the clinical management of PPROM are necessary.