The incidence of preterm birth in developed countries has steadily increased over the past two decades and now approaches 12.5% of all live births in the U.S. This is due, in part, to our incomplete understanding of the pathways that maintain uterine quiescence throughout pregnancy, as well as those that promote increased uterine contractility and cervical ripening leading to labour. It is clear that uterine quiescence throughout most of pregnancy is maintained by progesterone acting through its nuclear receptor (PR). Furthermore, there is increasing evidence that both preterm and term labour are associated with activation of inflammatory response pathways in the pregnant uterus and cervix. In this article, we will consider the factors that induce the inflammatory response leading to term and preterm labour. We also will review findings to support the novel concept that the maintenance of uterine quiescence vs. induction of uterine contractility is exquisitely controlled by the cross-repressive effect of progesterone/PR and inflammatory transcription factors, such as nuclear factor κB (NF-κB).