Adenosine Deaminases Acting on RNA (ADARs) are RNA editing enzymes that catalyze the hydrolytic deamination of adenosine (A) to inosine (I) in duplex RNA. In humans, two catalytically active ADARs, ADAR1 and ADAR2, perform this A-to-I editing reaction. The growing field of nucleotide base editing has highlighted ADARs as promising therapeutic agents while multiple studies have also identified ADAR1’s role in innate immunity and cancer. This presentation will introduce ADARs and A to I RNA editing along with a description of biochemical and structural studies that have advanced our understanding of ADARs’ reactivity and selectivity. In addition, I will describe how high throughput screening and chemical modifications can be used to optimize guide RNAs that can recruit ADARs for the correction of disease-causing mutations at the RNA level.