RNA’s increasing comprehension activities and pivotal involvement in diseases facilitate the utilization of various RNAs to specifically act on “undruggable” genes, proteins, and their transcripts, hence certainly expanding the domain of therapeutic targets. While several RNA-based medications are currently under investigation/clinical trial, some of them are undergoing preclinical studies. Furthermore, several methods have been developed to enhance the movement of RNA within cells and improve its stability in the body, despite the considerable difficulties encountered in developing therapies based on RNA. This chapter provides a detailed summary of the mechanisms of action, difficulties, solutions, and clinical use of RNA-based therapies.