Uterine decidualization, a key event in implantation, is critically controlled by stromal cell proliferation and differentiation. Although the molecular mechanism that controls this event is not well understood, the general consensus is that the factors derived locally at the site of implantation influence aspects of decidualization. Hoxa-10, a developmentally regulated homeobox transcription factor, is highly expressed in decidualizing stromal cells, and targeted deletion of Hoxa-10 in mice shows severe decidualization defects, primarily due to the reduced stromal cell responsiveness to progesterone (P(4)). While the increased stromal cell proliferation is considered to be an initiator of decidualization, the establishment of a full-grown functional decidua appears to depend on the aspects of regional proliferation and differentiation. In this regard, this article provides an overview of potential signaling mechanisms mediated by Hoxa-10 that can influence a host of genes and cell functions necessary for propagating regional decidual development.