Years of advances in high-throughput biotechnologies exemplified by nucleic acid sequencing and single-molecular imaging have led to our increasing capacity to interrogate genomes down to nucleotide accuracy with single-cell or even subcellular resolution, thereby gaining high-dimensional information on the genetic variants and epigenetic states associated with physiological and pathological processes. To achieve a causal understanding of the exquisite biology encoded in our genome, researchers in the past decades have sought to develop companion genome engineering tools. The ability to manipulate genetic information at similar resolution and genome-scale holds the promise to reveal fundamental insights into genomics research and has wide applications across many different fields. Technologies evolved from the naturally occurring Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) have emerged as a versatile platform to enable this goal through RNA-guided genome engineering. Here, researchers in the CRISPR genome-editing field have presented forward-looking reviews on different modalities and applications of this groundbreaking technology, with implications for basic biology, translational medicine, and beyond.