This chapter highlights the recent advancements in stem cell-based therapeutic applications in tissue repair/regeneration in experimental studies and, more recently, in the clinic. Translation of stem cell-based technology into clinical applications still faces the following formidable challenges: the risk of tumor formation, gene correction of induced pluripotent stem cells (iPS) from patients with genetic disease, and successful differentiation of iPS cells into target cell types. The chapter discusses the applications of DNA-based gene therapy to transplantation tolerance. It also focuses on the application of gene therapy to transplantation with particular focus on the direct manipulation of the transplant or graft recipient to promote long-term graft survival and induction of transplantation tolerance. Taken together, tissue regeneration, nanotechnologies, gene therapy, and VCA all represent some portion of the future of transplantation. They provide alternative sources of tissues and organs to meet the increasing demands in the field of transplantation.