Implantation in humans is a multistep process that involves apposition, adhesion, and invasion of the developing blastocyst into the receptive maternal endometrium. Though significant volume of research in this direction has identified important players orchestrating this delicate process, there are still gaps in our understanding of all the sequence of events during embryo implantation. Also, the early pregnancy-related complications that lead to fetal loss and miscarriage often occur in this critical window of implantation, which is primarily defined as the time when the maternal endometrium is supposed to be most receptive to the free blastocyst that emerges out from the zona pellucida. Studies in humans and rodents have identified several mediators like folliculin, LIF, IL11Rα, splicing factor SC35, etc. to be essential for early implantation. Trophoblasts, that form the outer epithelial layer of the blastocyst, participate in the formation of the placenta. During placentation, invasive extravillous trophoblasts (EVTs), migrate into the endometrium, and a transient epithelial to mesenchymal transition (EMT) and remodel the uterine arteries for blood and nutrient exchange.