Intra-amniotic infection and inflammation is a frequent and important cause of spontaneous preterm labor and delivery. Indeed, it is the only pathologic process for which both a causal link with spontaneous preterm birth has been established and a molecular pathophysiology defined. Fetal infection/inflammation has been implicated in the genesis of fetal and neonatal injury leading to cerebral palsy (CP) and chronic lung disease. Pathologic intra-amniotic inflammation can occur in the absence of detectable microorganisms using cultivation and molecular microbiologic techniques. This condition is known as sterile intra-amniotic inflammation and has been observed in patients with preterm labor and intact membranes, preterm PROM, and a short cervix. A mild sterile inflammatory process also participates in spontaneous labor at term, but this is considered to be an example of physiologic inflammation similar to that implicated in other important events in reproductive physiology, such as ovulation and implantation. Sterile pathologic inflammation has been implicated in gout, in which the danger signals are urate crystals and atherosclerosis. Thus, pathologic sterile inflammation is an important mechanism of disease.