CRISPR-Cas9 revolutionized the field of genetic engineering but has significant drawbacks, as the double-strand breaks it induces have a relatively high rate of mutations and off-target activity. An emerging alternative is NICER, a technique utilizing an endonuclease called nickase, which has much lower levels of mutagenicity and a high level of specificity that rivals CRISPR-Cas9. This review will survey the various developments made in the nickase pipeline, specifically how they make up for CRISPR’s drawbacks, and its potential for treating genetic disorders with more accuracy and efficiency than current therapeutic tools.