Mesenchymal stem cells (MSCs) are obtained from cell suspensions of total bone-marrow (BM) after culture. MSCs can negatively affect every step of the immune response from antigen presentation to the activation of T and B lymphocytes. The immunomodulatory effects of MSCs are employed for therapeutic purposes in the treatment of graft vs. host reactions and autoimmune diseases, as well as for improving HSC engraftment. More recently, nestin, a cell marker of neuroectoderm stem cells, was used to identify a new cell type in the BM stroma that could also correspond to in situ MSCs. This chapter presents examples of the clinical use of MSCs to summarize the problems and controversies rather than to provide a complete scope of the cell therapy with MSCs. It is necessary to obtain a significant improvement in the in vivo differentiation of these cells into other cell lineages, even those derived from the mesoderm.