Every ninth couple in Europe and USA is affected by implantation disorders and pregnancy wastage and majority of pregnancy losses occur before or during implantation. Therefore, understanding the cross talk between fetal and maternal components before, during and after their confrontations remains a major challenge. Human implantation may be described as a three steps process starting with the apposition and adhesion of a competent blastocyst to the endometrium epithelium and continuing by an extensive invasion throughout the first trimester of pregnancy in a receptive endometrium. The complex very highly reciprocal orchestrated process of human implantation leads to the essential construction of a haemochorial placenta. This chapter will detail the Human particularities of the implantation beginning by a maternal and paternal local preparation, a switch of the local immunity to establish transiently a local environment of immune tolerance. We will detail the role of hormone, cytokines, growth factors as well metalloproteases and transcription factors within this complex and evolutive dialogue.