Mesenchymal stem cells (MSC) are currently considered the most promising type of adult stem cells for therapeutic applications, because they can be easily isolated from the bone marrow and other tissues, and manipulated for different applications. The genetic transformation of MSC using genes that enhance their homing ability, as well as their proliferation and survival capacities when transplanted to sites of injury, is an important alternative to improve MSC function, especially for tissue regeneration. This chapter describes protocols for the transformation of MSC using plasmid vectors by lipofection and electroporation, as well as retroviral vectors representing viral transformations.