Trophoblasts and macrophages, the 2 major fetal-derived cells that comprise the placenta, play important roles in placental development and pregnancy maintenance. In response to hypoxia in early pregnancy, placental trophoblasts are required to differentiate into extravillous trophoblasts to ensure a good blood supply from the mother, and then into fused trophoblasts, which secrete placental hormones that contribute to placental growth. Placental Hofbauer cells are tissue macrophages found in the placenta throughout pregnancy. As phenotypically and functionally M2 macrophages, they have a wide range of roles, including phagocytosis of inflammatory substances in the placenta, angiogenesis for placental growth, and maintenance of immune tolerance in the placenta. In this review, we will discuss the functions and characteristics of trophoblasts and Hofbauer cells in the maintenance of immune tolerance of the placental villi and their applicability in perinatal research.