Ribonucleic acid (RNA) therapeutics are a novel category of therapeutic agents that use different types of RNAs to regulate genes and modulate protein synthesis to treat a wide range of diseases. The main advantages of RNA therapeutics over conventional small molecule drugs would be the potential to target undruggable sites, ease of production and faster development process, and longer duration of action. Various types of RNA therapeutics including antisense oligonucleotides (ASO), RNA interference (RNAi), small interfering RNA (siRNA), microRNA (miRNA), and messenger RNA (mRNA), have been developed and used for various clinical applications, especially for gene and vaccine delivery purposes. This review is focused on various therapeutic applications of RNA-based delivery systems and then siRNA technologies are discussed in more detail. Next, the FDA-approved siRNA therapeutics and those are in clinical trials are listed and summarized. Then, various viral and non-viral vectors used for RNA delivery purposes are discussed. Finally, clinical applications of siRNA therapeutics are reviewed in detail.