This article addresses the question of whether the uterine cavity is normally sterile and reviews the difficulties in conducting microbiologic studies of the endometrium, the limitations of conventional microbiologic techniques (cultivation-dependent), and the potential contribution of molecular microbiology to examine microbial diversity and burden of the endometrium. Issues pertaining to the diagnosis of chronic endometritis and the need for information about the prognostic value of this finding in subsequent pregnancies are discussed. The results of a randomized clinical trial of antibiotic administration versus placebo in women with a previous preterm birth are reviewed and commentary is provided. The emerging picture is that microbial-host interactions in the endometrial cavity are important for reproductive success. This is a US government work. There are no restrictions on its use.