Uterine natural killer (uNK) cells, sharing many characters with peripheral blood natural killer (pNK) cells, are a major uterine lymphocyte population at early gestational stages during normal pregnancy in placental mammals. The functions of uNK cells include cytokine production and cytotoxicity that are regulated by signals through activating and inhibitory receptors. UNK cells differ from pNK cells however and contribute to the structural changes that accompany the differentiation of the maternal-fetal interface. Immunological mechanisms must provide a balanced environment for uNK cell proliferation, differentiation and activation through intricate signaling pathways. An improved knowledge of mechanisms regulating uNK cells development and the cytokine network at the maternal-fetal interface of mice and humans might be useful to harness the power of these cells for maintenance of pregnancy.