The placenta is the first organ to form during mammalian embryogenesis. Problems in its formation and function underlie many aspects of early pregnancy loss and pregnancy complications in humans. Because the placenta is critical for survival, it is very sensitive to genetic disruption, as reflected by the ever-increasing list of targeted mouse mutations that cause placental defects. Recent studies of mouse mutants with disrupted placental development indicate that signalling interactions between the placental trophoblast and embryonic cells have a key role in placental morphogenesis. Furthering our understanding of mouse trophoblast development should provide novel insights into human placental function.