Preterm birth is the leading cause of infant morbidity and mortality. Very preterm births, those occurring before 32 completed weeks of gestation, are associated with the greatest risks. The leading cause of very preterm birth is intrauterine infection, which can lead to an inflammatory response that triggers labor or preterm premature rupture of membranes. How bacteria invade the uterine cavity, which is normally a sterile environment, and the reasons why different species vary in their capacity to induce inflammation and preterm birth are still incompletely understood. However, advanced techniques that circumvent the need for cultivating bacteria, deep sequence analysis that allows for the comprehensive characterization of the microbiome of a given body site and detection of low-prevalence species, and transcriptomics and metabolomics approaches that shed light on the host response to bacterial invasion are all providing a more complete picture of the progression from vaginal colonization to uterine invasion to preterm labor and preterm birth.