Animal models are a powerful tool to understand the mechanisms underlying physiological and pathological processes in vivo. To date, mice remain the species most commonly used for genetic manipulation. The recent development of engineered endonucleases such as Zinc Finger Nucleases (ZFN), Transcription activator-like effector nucleases (TALEN), and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) offered easy, flexible, and fast alternative to ES-Cell based gene targeting. Thanks to multiple advantages, the CRISPR system superseded its predecessors and became a popular method for genome editing. Here, we review the latest techniques to apply CRISPR editing to the mouse genome, and emphasize on the current methods used in transgenic laboratories and subsequent achievements in mice.