The potent immunomodulatory properties of mesenchymal stem cells (MSCs) are particularly relevant for multiple sclerosis (MS). MSCs inhibit T-cell proliferation stimulated by polyclonal activators, cognate antigen and allogeneic mixed lymphocyte reaction. MSCs inhibit B-cell proliferation in culture via soluble factors, accompanied by inhibition of B-cell differentiation and production of IgM, IgG, and IgA. The property of MSCs relevant to MS is their potential ability to lessen damage and augment repair in numerous tissue injury models. In general, MSC transplantation in humans, including with allogeneic MSCs, has been very well tolerated. The several potential adverse events (AEs) that require close attention in planned trials are: infusion-related toxicity, infection, cancer, ectopic tissue formation, rejection, and autoimmunity. MSCs have potential immunomodulatory, tissue protective, and repair promoting properties. There is rapidly accumulating experience with both autologous and allogeneic MSC transplantation in a number of conditions.