Decidualization of the endometrial stroma is a precondition for successful establishment of pregnancy. While the local molecular mechanisms driving decidualization are still largely unknown, a number of autocrine/paracrine factors have been identified as differentiation factors in this process. These include the cytokines, interleukin 11, activin A and monoclonal non-specific suppressor factor beta (MNSFbeta). Furthermore, locally produced proteases, including proprotein convertase 6 and matrix metalloproteinases, enable expansion of the tissue and processing of regulatory molecules. This article reviews recent work from our laboratory on the roles of these factors in decidualization.