Recent advances in RNA design and delivery have enabled the development of RNA-based medicine for a broad range of applications, including therapeutics, vaccines, and diagnostics. While human RNA medicine has faced many challenges in terms of efficacy and immunogenicity, the recent success of mRNA vaccines against COVID-19 and the approval of new RNA-based drugs provide new momentum to the field. Many classes of RNA play important regulatory roles in cells and tissues, beyond the obvious role of mRNA in protein synthesis. Scientific research, clinical development, and commercial production now focus on exploiting the many roles of RNA for use in biotechnology and medicine. Advances in understanding RNA structure and function are combined with a robust production pipeline to develop clinically effective RNA-related applications. Many key discoveries have contributed to the advancing of RNA medicines we have today. Early research in the 1950s on nucleic acids led to the discovery of mRNA. In the next decade, the 5'-cap on mRNA was discovered , the first liposome-entrapped RNA was delivered into cells , and antisense oligomers (ASOs) were used to inhibit respiratory syncytial virus (RSV) . In the 1980s, in vitro transcription from engineered DNA templates using a bacteriophage SP6 promoter and RNA polymerase allowed the manufacture of mRNA and expression of other types of RNA in cell-free systems. Later in the 1980s, the first cationic-lipid mediated mRNA delivery was achieved . The discovery of RNA interference (RNAi) and the approval of the first antisense RNA drug in the late 1990s were key to the development of RNA therapeutics. For their pioneering work on RNAi and the RNA-induced silencing complex (RISC) , Fire and Mello were awarded the Nobel Prize in Physiology and Medicine in 2006. During the 2000s, the discovery of the importance of pseudouridine modification and further research on mRNA led to the first human trial of an mRNA vaccine against melanoma in 2008 . In 2010, a pivotal human clinical trial showed that siRNA could target specific human genes , and subsequent pre-clinical research and development led to the approval of the first siRNA drug in 2018 . Most recently, Doudna and Charpentier were awarded the Nobel Prize in 2020 for CRISPR/Cas9 gene editing. Two human mRNA vaccines against COVID-19 received Emergency Use Authorization in 2020 and one of them was finally approved in 2021 . These key milestones and achievements are captured in Figure .