Nature Reviews Nephrology, Published online: 09 October 2025; doi:10.1038/s41581-025-01011-7Progress in the development of RNA-based therapeutics has been accelerated by the identification of organ-enriching carriers and cell-specific targeting conjugates, leading to their approval for a range of indications. However, attempts to develop RNA-based therapeutics for kidney diseases have proved challenging. This Review describes the physiological, technological and pharmacological hurdles that need to be overcome to realize the potential of RNA therapeutic approaches to kidney diseases.