<p>In the past decade, RNA-based therapeutic strategies have transitioned from drugs of promise to transformative treatments for a range of previously untreatable diseases. This transition has largely been driven by a growing comprehension of individual cell types and corresponding transcriptomes in healthy and diseased tissues. However, despite their natural and abundant distribution to the kidney, successful RNA-based therapeutics for kidney diseases are scarce, as the overwhelming majority of administered drugs are either rapidly excreted, localize to non-targeted cells or are unproductive owing to endolysosomal compartmentalization. The limited success in developing RNA-based therapies for this vital organ have led to considerable doubt regarding the targetability and suitability of splice modulation, small interfering or activating RNAs, microRNA mimics or antagonists, aptamers or editing strategies for the treatment of kidney diseases. Strategies to target specific cell types within the kidney and improve the productive uptake of RNA-based drugs are needed to improve the therapeutic efficacy and safety of RNA-based therapies. Despite these challenges, a number of RNA-based therapeutic approaches are being explored for a variety of kidney diseases and hold promise for future validation.</p>