The human placenta is characterized by the intensity of the trophoblast invasion into the uterus wall and the specificity of its hormonal functions. Placental hormones are required for the establishment and maintenance of pregnancy, adaptation of the maternal organism to pregnancy and fetal growth. In the early placenta at the maternofetal interface, the human trophoblast differentiates along two pathways: 1/ the villous trophoblast pathway including the cytotrophoblastic cells which differentiate by fusion to form the syncytiotrophoblast that covers the entire surface of the villi; 2/ the extravillous trophoblast pathway. The cytotrophoblastic cells of the anchoring villi in contact with the uterus wall proliferate and then migrate into the decidua and the myometrium but also participate to the remodeling of the spiral arteries. During the first trimester of pregnancy the spiral arteries are plugged by trophoblastic cells, allowing the development of the fetoplacental unit in low oxygen environment. At this stage of pregnancy the extravillous trophoblast secretes a large amount of hormones such as particular hyperglycosylated forms of hCG directly involved in the quality of the placentation. At 10-12 weeks of pregnancy, the trophoblastic plugs are progressively dislocated and the syncytiotrophoblast starts to bath in maternal blood. It secretes the major part of its polypeptide hormones in maternal circulation taking over the maternal metabolism in order to increase the energetic flux to the fetus. As example the placental GH (growth hormone) secreted continuously by the syncytiotrophoblast is directly involved in the insulino-resistance of pregnancy. Capturing the cholesterol from the maternal lipoproteins, the syncytiotrophoblast synthesizes also large amount of progesterone essential for the uterine quiescence. Deprived of cytochrome P450 17alpha-hydroxylase-17:20 lyase, it uses the maternal and fetal adrenal androgens to synthesize estrogens. The differentiation and hormonal functions of the human trophoblast are regulated by the environmental O2 and reflect mammalian evolution.