The survival of allogeneic fetuses during pregnancy is a rather paradoxical phenomenon with a complex mechanism. Chemokine ligand12 (CXCL12) and its receptors CXC chemokine receptor (CXCR)4 and 7 are extensively found in placenta tissues and cells, including trophoblast cells, vascular endothelial cells, and decidual stromal and decidual immune cells (eg, NK cells and regulatory T cells). Evidence has illustrated that the CXClL12/CXCR4/CXCR7 axis could enhance the cross talk at the maternal‐fetal interface through multiple processes, such as invasion and placental angiogenesis, which appears to be critical signaling components in placentation and fetal outcome. In addition, an increasing number of studies have demonstrated that the CXCL12/CXCR4/CXCR7 axis also stands out for its pleiotropic roles in several pregnancy‐associated diseases (eg, recurrent spontaneous abortion (RSA), pre‐eclampsia (PE), and preterm labor). In the present review, the different biological properties and signaling in physiological and pathological pregnancy conditions of CXCL12/CXCR4/CXCR7 axis were discussed, with the aim of obtaining a further understanding of the regulatory mechanisms and highlighting their potential as a target for therapeutic approaches.