In recent years mesenchymal stromal cells (MSC) have emerged as a major new form of cell therapy. While the original perception was that MSC were stem/progenitor cells with the potential to contribute to the regeneration of tissue, more recent data suggest that the principal mechanism of MSC activity is through the release of soluble mediators that elicit the observed biologic response. Future studies are needed to identify more completely the spectrum of therapeutic applications and delineate better the associated molecular and cellular mechanisms.