The human MHC class I molecule HLA-G has long been known as a molecule selectively expressed by cytotrophoblastic cells. By inhibiting the cytolytic function of decidual NK cells, HLA-G protects the HLA-A and -B negative semiallogeneic embryonic tissue against the mother's immune system. In the light of this immuno-suppressive function, the role of HLA-G in transplantation was investigated. We will review here recently published data on this topic, showing that expression of HLA-G affects the responsive capacity of the immune system, might directly participate in graft acceptation, and should be taken into account for the monitoring of transplantation patients.