The clustered regularly interspaced short palindromic repeat (CRISPR) associated 9 (Cas9) system is a microbial adaptive immune system that has been recently developed for genomic engineering. From the moment the CRISPR system was discovered in Escherichia coli, the drive to understand the mechanism prevailed, leading to rapid advancement in the knowledge and applications of the CRISPR system. With the ability to characterize and understand the function of the Cas9 endonuclease came the ability to adapt the CRISPR-Cas9 system for use in a variety of applications and disciplines ranging from agriculture to biomedicine. This review will provide a brief overview of the discovery and development of the CRISPR-Cas9 system in applications such as genome regulation and epigenome engineering, as well as the challenges faced.