Multipotent mesenchymal stromal cells (MSCs) are able to differentiate in vitro into adipocytes, osteoblasts and chondrocytes and into bone in vivo. MSCs have now been isolated from multiple organs and they form part of the endothelial wall of blood vessels. MSCs are emerging as vehicles for anticancer drug/gene delivery. This chapter aims to dissect this observed discrepancy in different experimental settings of human cancer so as to provide possible guidance to the appropriateness of clinical applications. MSCs were initially identified by placing whole bone marrow cells in plastic culture dishes and observing the subsequent expansion of a rare population of plastic‐adherent cells. MSCs tend to be recruited by injured tissue, where they are thought to contribute to tissue repair and wound healing. The tumor microenviroment is substantially different from that of normal organs and this is a mechanism in cancer development.