During the last 20 years there have been major improvements in renal replacement therapy, including dialysis and kidney transplantation; however, the treatment options for renal diseases are still limited. Gene therapy is a potential modality for many renal diseases for which we are as yet unable to offer specific treatment. This article reviews the recent data on gene therapy in animal models applicable to human renal diseases and evaluates its efficacy, safety and clinical relevance. Several approaches appear to be promising, including adeno-associated viral vectors for long-term gene expression, electroporation for muscular gene delivery, ultrasound/microbubble-mediated gene targeting, macrophage-based gene therapy and small interfering RNAs.