Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 is a genome-editing technology, that utilizes archaeal and bacterial Cas9 nucleases to introduce double-stranded breaks in DNA at targeted sites. These breaks can be used to remove, replace, or add pieces of DNA. While not the first genome editor, CRISPR-Cas9 is efficient and cost-effective because cutting is guided by a strand of RNA rather than a protein. The potential uses in health care are plentiful, from disrupting dominant genes that cause cancer to repairing mutated genes that cause genetic diseases, such as muscular dystrophy. Therapeutic approaches based on this technology fill the preclinical pipeline, and rely on the use of viral vectors to deliver the Cas9 gene and guide RNA to a gene of interest. However, concerns regarding the safety and efficacy of CRISPR-Cas9 use in gene therapy remain. A pre-print released prior to peer review has recently underlined the question of whether immunological responses to Cas9 may negatively impact its clinical use. Here we discuss the implications of this finding for the application of CRISPR/Cas in gene therapy.