Embryonic development is a complex process that is regulated by many cell types and signaling pathways. This review focuses on the role of NK cells and regulatory T-cells (Treg cells) in embryonic loss. Approximately 70% of uterine leukocytes until the time of mid-gestation are found to be CD16(-)CD56(bright) NK cells. This subset of NK cells, along with Treg cells, has been shown to regulate fetal development. We recently found a population of NK cells in the pregnant mouse uterus with a unique CD3(-)CD49b(+)CD25(+)Foxp3(+) phenotype. This review summarizes the studies indicating critical roles for expression of IL-10 by CD3(-)CD49b(+)CD25(+)Foxp3(+) cells and CXCR4 expression on CD16(-)CD56(bright) NK cells in preventing embryonic loss. In addition, the roles of toll-like receptors (TLRs) and CXCR4 in NK cell migration and functional modulation are discussed.