Until now there is no renal gene therapy available for clinical use, however, gene therapy for several experimental renal diseases has been tested with promising results. The kidney is a well-differentiated organ with a variety of specialized compartments, i.e., vascular, glomerular, tubular, and interstitial. Many physiological factors such as cell turnover rate, blood flow, and urine flow, as well as anatomical factors such as glomerular basement membrane and nephron segment arrangement, may affect the specificity and efficacy of gene therapy in the kidney. On the other hand, the kidney has a major advantage over other solid organs, since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the urinary tract, direct injection into renal parenchyma, and perfusion into the donor graft prior to transplantation (1 ). This chapter reviews nonviral gene transfer in the different compartments of the kidney (for review of viral vectormediated renal gene transfer, see refs. 2 –5 ), and in skeletal muscle, for renal gene therapy, and potential applications and safety concerns for renal gene therapy.