Recent advances in our understanding of RNA biology have uncovered crucial roles 
for RNA in multiple disease states, ranging from viral and bacterial infections 
to cancer and neurological disorders. As a result, multiple laboratories have 
become interested in developing drug-like small molecules to target RNA. 
However, this development comes with multiple unique challenges. For example, 
RNA is inherently dynamic and has limited chemical diversity. In addition, 
promiscuous RNA-binding ligands are often identified during screening campaigns. 
This Tutorial Review overviews important considerations and advancements for 
generating RNA-targeted small molecules, ranging from fundamental chemistry to 
promising small molecule examples with demonstrated clinical efficacy. 
Specifically, we begin by exploring RNA functional classes, structural 
hierarchy, and dynamics. We then discuss fundamental RNA recognition principles 
along with methods for small molecule screening and RNA structure determination. 
Finally, we review unique challenges and emerging solutions from both the RNA 
and small molecule perspectives for generating RNA-targeted ligands before 
highlighting a selection of the "Greatest Hits" to date. These molecules target 
RNA in a variety of diseases, including cancer, neurodegeneration, and viral 
infection, in cellular and animal model systems. Additionally, we explore the 
recently FDA-approved small molecule regulator of RNA splicing, risdiplam, for 
treatment of spinal muscular atrophy. Together, this Tutorial Review showcases 
the fundamental role of chemical and molecular recognition principles in 
enhancing our understanding of RNA biology and contributing to the rapidly 
growing number of RNA-targeted probes and therapeutics. In particular, we hope 
this widely accessible review will serve as inspiration for aspiring small 
molecule and/or RNA researchers.