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Stem cell therapies offer enormous hope for treating many tragic diseases and tissue defects. In particular, mesenchymal stem/multipotent stromal cells (MSCs) are capable of differentiating into multiple types of connective tissues (i.e., bone, cartilage, and even muscle and neuron) and have proangiogeneic and immunomodulatory effects. MSCs have potential utility for treating a variety of diseases and disorders, including graft versus host disease, problems related to organ transplantation, cardiovascular disease, brain and spinal cord injury, lung, liver, and kidney diseases, and skeletal injuries. This chapter summarizes the current status of therapeutic applications of MSCs. It begins by introducing the basics of MSCs and then focuses on their therapeutic potential, including mechanism of action, delivery routes, MSC homing, the current status of clinical trials, and potential challenges and safety issues. Finally, the chapter describes chemical approaches developed in the authors’ laboratory to promote homing and engraftment of systemically infused MSCs within specific tissues.