CRISPR technology is rapidly evolving, and the scope of CRISPR applications is constantly expanding. CRISPR was originally employed for genome editing. Its application was then extended to epigenome editing, karyotype engineering, chromatin imaging, transcriptome, and metabolic pathway engineering. Now, CRISPR technology is being harnessed for genetic circuits engineering, cell signaling sensing, cellular events recording, lineage information reconstruction, gene drive, DNA genotyping, miRNA quantification, in vivo cloning, site-directed mutagenesis, genomic diversification, and proteomic analysis in situ. It has also been implemented in the translational research of human diseases such as cancer immunotherapy, antiviral therapy, bacteriophage therapy, cancer diagnosis, pathogen screening, microbiota remodeling, stem-cell reprogramming, immunogenomic engineering, vaccine development, and antibody production. This review aims to summarize the key concepts of these CRISPR applications in order to capture the current state of play in this fast-moving field. The key mechanisms, strategies, and design principles for each technological advance are also highlighted.