The article discusses the challenges and potential solutions in the therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), for the treatment of various diseases. While RNA-based therapeutics, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and other agents, have shown promise in clinical trials, their efficacy and safety have been mixed. The authors highlight key challenges, such as specificity, delivery, and tolerability, and explore emerging approaches to enhance the success of ncRNA therapeutics. These include the use of "tiny" antisense RNAs, metronomic therapy, combinatorial RNA therapeutics, and small-molecule inhibitors of miRNAs. The article also reviews the biogenesis of miRNAs and ways to interfere with this process therapeutically, as well as the potential of targeting ncRNAs with interaction element blockers and structural element lockers. Finally, it discusses the application of RNA-based therapeutics in treating RNA viruses, particularly in the context of the ongoing COVID-19 pandemic.The article discusses the challenges and potential solutions in the therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), for the treatment of various diseases. While RNA-based therapeutics, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and other agents, have shown promise in clinical trials, their efficacy and safety have been mixed. The authors highlight key challenges, such as specificity, delivery, and tolerability, and explore emerging approaches to enhance the success of ncRNA therapeutics. These include the use of "tiny" antisense RNAs, metronomic therapy, combinatorial RNA therapeutics, and small-molecule inhibitors of miRNAs. The article also reviews the biogenesis of miRNAs and ways to interfere with this process therapeutically, as well as the potential of targeting ncRNAs with interaction element blockers and structural element lockers. Finally, it discusses the application of RNA-based therapeutics in treating RNA viruses, particularly in the context of the ongoing COVID-19 pandemic.