This chapter explores the complicated immune mechanisms at play during pregnancy by focusing on the role of immune checkpoints in maintaining maternal-fetal tolerance. It begins by introducing the concept of the fetus as a semi-allogeneic graft and the necessity for immune modulation during pregnancy. The chapter then explores the components of the maternal-fetal interface, including the decidua and placenta, and discusses the various immune cells involved in pregnancy, such as T cells, NK cells, and macrophages. A major part of the chapter is dedicated to examining the expression and function of key immune checkpoint molecules, including PD-1, CTLA-4, TIM-3, TIGIT, and LAG-3, in the context of normal pregnancy and pregnancy complications. The chapter also addresses the implications of immune checkpoint dysregulation in miscarriage and recurrent pregnancy loss. To summarize, the chapter highlights the delicate balance required in the maternal immune system to protect against pathogens while maintaining tolerance to the fetus and emphasizes the potential of immune checkpoints as targets for understanding and potentially treating pregnancy-related disorders.