There is considerable interest in mesenchymal stem cell biology. This relates, in part, to the possibility that such cells could be used to replace tissues in degenerative diseases of mesenchyme. In this article, the current status of the field is discussed, highlighting technical and theoretical issues related to the identification, isolation, and characterization of these cells. Our focus is the endogenous noncirculating mesenchymal stem cell populations that normally reside in adult organs.