Tissues and organs harbor a component of supportive mesenchymal stroma. The organ stroma is vital for normal functioning since it expresses factors instructing growth and differentiation along with molecules that restrain these processes. Similarly, the growth of tumors is strictly dependent on the tumor stroma. This review first discusses the possibility of developing tools to block the propagation of the tumor-associated stroma, that may halt tumor progression. It further describes how the tropism of mesenchymal stroma to tumor sites may be utilized to cause regression of the cancerous tissue. Mesenchyme can be genetically modified to overexpress specific regulatory molecules with known effects on specific tumors, such as interferon beta, studied in the context of melanoma and glioma and activin A, a transforming growth factor beta cytokine, examined in multiple myeloma. These studies point to the possibility that genetically modified mesenchymal cells may be used as a therapeutic modality for incurable human diseases. It is proposed that further development of methods of tumor stroma targeting, or alternatively the use of stromal mesenchyme as a cell or cell/gene therapy modalities, may yield novel clinical tools for the treatment of human cancers.