Mesenchymal stem cells, cautiously re-named recently multipotent mesenchymal stromal cells (MSCs) because of their heterogeneous multipotency at single cell level and their similarities with fibroblasts, have been strongly suggested in the last decade as powerful inhibitory cells for the vast majority of immune effector cells. The redundancy of the molecular pathways involved in the immune modulation suggests that this property, shared by MSCs of different tissue origin, including lymphoid organs, and by fibroblasts, has a pivotal role in tissue homeostasis in normal and pathological inflammatory reactions.