Mesenchymal stem cells (MSC) are found in a variety of tissues, including bone marrow, skin and adipose tissue and can be expanded easily in vitro. MSC are thought to have tissue regenerative properties, in the first place via their multilineage differentiation capacity. In addition, MSC have potent immunomodulatory capacity. They inhibit the proliferation of T cells and inhibit dendritic cell maturation. These properties make MSC promising for a diversity of clinical applications; for example, for the prevention and treatment of autoimmune diseases and bone marrow rejection. Different studies have attributed the immunosuppressive effect of MSC to different immunosuppressive factors. These include indoleamine 2,3-dioxygenase (IDO), HLA-G, nitric oxide, interleukines. The long-term ability of allogeneic MSCs to preserve function in the infarcted heart is limited by a biphasic immune response whereby they transition from an immunoprivileged to an immunogenic state after differentiation, which is associated with an alteration in major histocompatibility complex--immune antigen profile. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders.