Placentation in humans is precocious and highly invasive compared to other mammals. Implantation is interstitial, with the conceptus becoming completely embedded within the endometrium towards the end of the second week post-fertilization. Villi initially form over the entire surface of the chorionic sac, stimulated by histotrophic secretions from the endometrial glands. The secondary yolk sac never makes contact with the chorion, and a choriovitelline placenta is never established. However, recent morphological and transcriptomic analyses suggest that the yolk sac plays an important role in the uptake of nutrients from the coelomic fluid. Measurements performed in vivo demonstrate that early development takes place in a physiological, low-oxygen environment that protects against teratogenic free radicals and maintains stem cells in a multipotent state. The maternal arterial circulation to the placenta is only fully established around 10-12 weeks of gestation. By then, villi have regressed over the superficial, abembryonic pole, leaving the definitive discoid placenta, which is of the villous, hemochorial type. Remodeling of the maternal spiral arteries is essential to ensure a high-volume but low-velocity inflow into the mature placenta. Extravillous trophoblast cells migrate from anchoring villi and surround the arteries. Their interactions with maternal immune cells release cytokines and proteases that are key to remodeling, and a successful pregnancy.