Recently, stem cell research has attracted considerable attention because it could be used for the regeneration of damaged organs that are untreatable by conventional techniques, and several stem cells (or progenitor cells), such as endothelial stem cells and neural stem cells have been discovered. Following the progression of this field of research, the potential for stem cell gene therapy has increased and several therapeutic benefits have already been reported. Although this approach was originally investigated for fatal or hereditary diseases, chronic renal failure is also a candidate for stem cell gene therapy. We have proposed two different therapeutic strategies for chronic renal failure depending on whether the bone marrow stem cells differentiate and commit into mesenchymal or hematopoietic stem cells. In the case of diseases, which need reconstitution of residential renal cells, such as congenital enzyme deficiency diseases, mesenchymal stem cells should be transplanted, and in contrast, hematopoietic stem cells may be used for gene delivery for diseases, which need foreign cytokines and growth factors, such as glomerulonephritis. This article reviews the recent investigation on this tailor-made stem cell gene therapy for chronic renal failure and discusses the potential of this novel strategy and the major practical challenges of its clinical application.