The trophoblast begins at the outer covering of the early blastocyst. They provide the route of nourishment between the maternal endometrium and the developing embryo. The trophoblast adhesion to the uterine wall is the requisite first step of implantation and, subsequently, placentation. Human villous trophoblasts (HVT) covering the villi of the placenta provide the surface for the exchange of oxygen and nutrients with the maternal circulation. They synthesize and release chorionic gonadotropin, placental lactogen and angiogenin and express CXCR4, CCR5 and also prolactin gene family. They acquire CCR1 as they differentiate to an invasive phenotype at the villous-anchoring sites. The features of HVT make them an ideal genetic platform to study cell differentiation and organogenesis. They are also useful tools to develop disease models for High Throughput and High Content Screening.