Novel cell-based and gene therapies represent promising approaches for the treatment of incurable diseases, including cancer. Following the success of the hematopoietic stem cell-based transplantation, other populations of adult progenitor cells, including mesenchymal stem cells (MSCs), have been identified as powerful therapeutic tools in humans. The intrinsic capability of MSCs to migrate toward injured tissues emphasizes their suitability to deliver anticancer agents for new clinical applications in addition to the tissue repairing capacity. Here, we revisit the experimental history of MSCs, the most exciting features of their biology in keeping with their promising applications in cell-based therapeutic strategies for cancer treatment.