Mesenchymal stem cells (MSCs) are multipotent cells that can self-renew and differentiate into cells of all germ layers. MSCs can be easily attracted to the site of tissue insult with high levels of inflammatory mediators. The general ability of MSCs to migrate at the sites of tissue injury suggested an innate ability for these cells to be involved in baseline tissue repair. The bone marrow is one of the primary sources of MSCs, though they can be ubiquitous. An attractive property of MSCs for clinical application is their ability to cross allogeneic barrier. However, alone, MSCs are not immune suppressive cells. Rather, they can be licensed by the tissue microenvironment to become immune suppressor cells. Immune suppressor functions of MSCs include those that blunt cytotoxicity of natural killer cells, suppression of T-cell proliferation, and “veto” function. MSCs, as third-party cells, suppress the immune response that generally recapitulates graft-versus-host disease (GvHD) responses. Based on the plastic functions of MSCs, these cells have dominated the field of cell-based therapies, such as anti-inflammatory and drug delivery. Here, we focus on the potential use of MSC for immunological disorders such as Crohn’s disease and GvHD.