Kidney transplantation represents the therapy of choice for many patients with end-stage renal disease. However, the success of renal engraftment is hindered by a number of factors, the most important of which being adverse effects of systemic immunosuppressive therapy, chronic transplant dysfunction and a severe shortage of donor kidneys. Gene therapy approaches may provide valuable strategies in each of these areas. First, gene therapy holds the potential of local therapy, thus circumventing systemic side effects of chronic immunosuppression. Second, chronic transplant dysfunction may be addressed by innovative strategies to induce local immune tolerance, immune suppression and additional graft protecting mechanisms. Third, gene therapy may be instrumental in increasing the quality of the grafts by limiting ischemia-reperfusion injury, especially in non-heart beating donors, thereby expanding the donor pool. In this article, we give an overview of the current state of gene therapy in experimental models of kidney transplantation.