Premature delivery results from multiple closely interdependent factors. Inflammation is most generally caused by cervicovaginal infection that may progress to intra-uterine infection or inflammation. Severe chorioamniotitis is found in 75% of all premature deliveries compared with 15% in term deliveries. Premature rupture of the membranes is the cause of premature delivery in 30-40% of premature deliveries although the diagnosis of chorioamniotitis can also be established with intact membranes, sometimes on the basis of histological findings alone. The degree of prematurity is correlated with the severity of the histological chorioamniotitis. The severity and the duration of the lesions is often the cause of antibiotic failure for the treatment of threatening premature delivery. Inflammation mediators, mainly proinflammatory cytokines (IL1, TNF-alpha), chemokines (IL6, IL8 and MIP-1alpha) and immunomodulator cytokines (IL6) and immunosuppressive cytokines (IL10, IL4) are produced by the amniotic and decidual membranes and are found in the fetal circulation and amniotic fluid. This reaction triggers a cascade of events leading to the production of prostaglandins and cyclooxygenase (COX2) activity, that cause uterine contractions. The inflammation may be initiated locally, even from an extrapelvic location, This leads to a fetal and/or maternal systemic inflammatory reaction. Systemic fetal expression of deregulated inflammatory phenomena can lead to neonatal lesions of lung and brain white matter tissue. This explains the failure of tocolysis and antibiotics in uncontrolled situations and suggests new avenues for therapy using selective inhibitors of COX2.