NK cell effector function is regulated by a range of activating and inhibitory receptors, and many of their known ligands are MHC class I molecules. Human NK receptors encoded by the Killer immunoglobulin-like receptor (KIR) gene family recognize polymorphic HLA-C as well as some HLA-A and HLA-B molecules. KIRs are expressed by uterine NK (uNK) cells, which are distinctive NK cells directly in contact with the invading fetal placental cells that transform the uterine arteries during the first trimester. Trophoblast cells express both maternal and paternal HLA-C allotypes and can therefore potentially interact with KIRs expressed by uNK. Therefore, allorecognition of paternal HLA-C by maternal KIR might influence trophoblast invasion and vascular remodeling, with subsequent effects on placental development and the outcome of pregnancy. We discuss here the studies relating to KIR/HLA-C interactions with an emphasis on how these function during pregnancy to regulate placentation.