The genome is said to represent the blueprint of life. However, it is highly dynamic, and the encoded instructions can be modified either permanently in the DNA or transiently in the RNA. For example, deaminases like ADARs can install single-base changes in these instructions. Moreover, the emergence of CRISPR technologies has ushered in a new era in cell engineering. Today, many biomedical and biotechnological applications, including gene therapy, are enabled by the ease at which CRISPR-Cas systems can be programmed to target any specific site in the genome or transcriptome. In this talk, I will outline how the field has evolved over the years and share some of our work on the development and application of new CRISPR- and ADAR-based tools to manipulate DNA and RNA in vitro and in living cells.