Uterine and peripheral natural killer (NK) cells represent phenotypically and functionally distinct populations. Decidual NK cells resemble the CD56(bright) peripheral NK subset in their CD56(bright) CD16(neg) phenotype but, unlike the peripheral population, they contain cytotoxic granules. The activity of NK cells is regulated by the expression of activating or inhibitory receptors on NK cells and by that of major histocompatibility complex class I molecules on target cells. The embryonic trophoblast that forms the interface between the maternal and fetal compartments expresses non-classical human leukocyte antigens that serve as ligands for NK receptors. Decidual NK cells fulfil dual tasks. During normal conditions they contribute to creating a favourable environment for placentation, but at the same time they are equipped with cytotoxic potential to fight intrauterine infections. Decidual NK activity is regulated by a complex, mutually interacting network of cytokines and hormones.