Small molecules targeting RNA represent a transformative frontier in drug discovery and offer new therapeutic options for diseases previously considered incurable.[1] This review article reviews recent advances in the development of small RNA-binding molecules, with an emphasis on obstacles and promising directions for future research.[1] Innovations in the determination of RNA structures include X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy, which form the basis for rational drug design.[1] Computational approaches, such as deep learning and molecular docking, improve the prediction of RNA structures and the efficiency of ligand screening.[1] Specialized libraries, DNA-encoded libraries, and small molecule microarrays, along with fragment drug discovery, are used to identify bioactive ligands.[1] The article reviews emerging strategies, such as RNA degraders and modulators of RNA-protein interactions, for their therapeutic potential.[1] Artificial intelligence and machine learning are accelerating the discovery and optimization of RNA-targeted drugs.[1] These advances aim to revolutionize the treatment of a wide range of diseases, including cancer, neurodegeneration and viral infections.[1][2]