The CRISPR (Clustered, Regularly Interspaced, Short Palindromic Repeats)-Cas (CRISPR-associated) (CRISPR-Cas) system has become trendy as it is suitable for numerous applications such as gene knockouts, genome-engineering, to name but a few. In a recent Technical Bulletin, Ed Davis describes the mechanism of CRISPR-Cas for genome editing and how the recent experimental improvements improve CRISPR-Cas9 specificity while reducing off-target effects.