Viruses are a therapeutic challenge since their life cycles occur within the host cells and often utilize cellular proteins and hence it is harder to identify therapeutic targets compared to bacteria, which have their own cellular metabolism that is quite different from the host and often present unique targets such as enzymes, etc. Nevertheless, viral proteins may present useful targets for therapy, e.g., small molecule inhibitors of viral polymerases, or prevention, e.g., viral coat proteins for vaccination. However, some viruses may enter an inactive state of persistence or latency where no or very few viral proteins are produced. Thus, methodologies that are specifically able to target nucleotide sequences within viral genomes would be a useful addition to the antiviral armamentarium. Such a methodology is the clustered regulatory interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, which is effective, specific, and versatile and provides unprecedented control over genome editing. Here, we will discuss how CRISPR/Cas9 has been used against human viruses and future prospects for novel therapeutic approaches.