In industrialized and developing countries, preterm birth (live delivery before 39 weeks of gestation) is both a leading cause of neonatal death and a major risk factor for respiratory, neurological, and cognitive disabilities in those infants who survive to adolescence. Intrauterine infection is considered a leading cause of preterm birth; data from clinical and experimental studies suggest that in utero infection accounts for upward of 40% of preterm deliveries. This chapter is written with two aims: the first is to provide the reader with an introduction to infection-associated preterm birth, highlighting the importance of animal-based studies in the development of this field; and the second, adopting a practical focus, is designed to provide the reader with technical insight into the use of sheep as a model organism for the study of fetal inflammatory responses to the presence of microbial agonist in the uterine sphere.