In mammals, pregnancy is an irreversible and complicated event. The mammalian uterus requires many physiological and morphological changes for pregnancy-associated events including implantation, decidualization, placentation and parturition. The failure to complete any events results in implantation failure, spontaneous miscarriage or abnormal parturition, including preterm birth. These events are primarily regulated by ovarian estrogen and progesterone (P4). P4 and estrogen are produced in the ovary throughout pregnancy in mice, but in humans, hormonal support switches from the ovary to the placenta. The first direct interaction between embryo and uterus is implantation. In humans, about 75% of unsuccessful pregnancies are believed to result from defective implantation. Therefore, a better understanding of the molecular mechanisms associated with implantation would be helpful for the further improvement of clinical treatments. Recent studies using genetically modified mice have given us considerable insight into the molecular mechanisms underlying embryo implantation. In this review, we discuss in the understanding recent advances of the molecular events during implantation, especially focusing on the roles of estrogen and P4 signaling. We also offer our thoughts on the as yet unelucidated processes in implantation to guide and stimulate further research in this area.