In murine and human pregnancies, embryos implant by attaching to the luminal epithelium and invading into the stroma of the endometrium. Under the influence of the steroid hormones estrogen and progesterone, the stromal cells surrounding the implanting embryo undergo a remarkable transformation event. This process, known as decidualization, is an essential prerequisite for implantation. It comprises morphogenetic, biochemical, and vascular changes driven by the estrogen and progesterone receptors. The development of mutant mouse models lacking these receptors has firmly established the necessity of steroid signaling for decidualization. Genomic profiling of mouse and human endometrium has uncovered a complex yet highly conserved network of steroid-regulated genes that supports decidualization. To advance our understanding of the mechanisms regulating implantation and better address the clinical challenges of infertility and endometrial diseases such as endometriosis, it is important to integrate the information gained from the mouse and human models.