This chapter examines the role of the unique cells of the placenta, the trophoblast, in the establishment of the placenta. It discusses the changes trophoblasts induce in the uterine environment. Recent evidence suggests that premature exposure of the placenta to maternal blood is likely to result in miscarriage. Subcellular trophoblast micro and/or nano particles are found in the maternal blood in both normal and pre eclamptic pregnancies with possibly increased quantities in pre-eclampsia. Deported trophoblasts may play a key role in the success of pregnancy via their effects on the maternal immune system. Antiphospholipid antibodies (aPL) are associated with thrombotic disease of the systemic circulation and were originally thought to induce recurrent miscarriage by causing thrombosis of the spiral arteries with subsequent infarction of the regions of the placenta supplied by the affected vessels. Heparin and aspirin therapy was introduced for women with recurrent miscarriage and aPL.