Emerging technologies allow us to read, write, and edit genomes with unprecedented efficiency and precision. Using CRISPR and single-cell technologies, we’ve generated thousands of genetic readouts to comprehensively map function-based enhancer-target gene interactions and chart biological processes. In addition, gene editing technologies we dissected the effects of thousands of single nucleotide variants in a genome-wide manner to understand natural and disease associated genetic variability. As we pursue such approaches in precision health, we are ever conscious of the off-target mutations or unintended repair outcomes resulting from CRISPR technologies, and present methods to measure and enhance editing efficiency and precision.