Mesenchymal stromal cells (MSC) are a population of phenotypically heterogeneous cells that can be isolated from many readily accessible tissues, including bone marrow, umbilical cord, placenta and adipose tissue, where they form part of the supportive, stromal micro-environment. Extensive ex vivo and pre-clinical data suggest that subpopulations within MSC contribute to immunomodulation of the host, without provoking immunologic responses from alloreactive T cells or other effector cells, as well as contributing to tissue repair. These unique properties make MSC an ideal investigational agent for treating graft-versus-host disease (GvHD). Therapeutic trials with varied MSC dosing schedules and clinical end-points have shown mixed results. We have reviewed the biology of MSC gleaned from pre-clinical models, and summarized the results of clinical trials utilizing MSC for the treatment of acute and chronic GvHD.