The emergence of the COVID-19 pandemic has starkly exposed our significantly limited ability to promptly identify and respond to emergent biological threats. Consequently, there is an urgent need to advance biotechnological methods for addressing both known and unforeseen biological hazards. Recently, the CRISPR/Cas system has revolutionized genetic engineering, enabling precise and efficient synthetic biology applications. Therefore, this review aims to provide a comprehensive introduction to the fundamental principles underlying the CRISPR/Cas system and assess the advantages and limitations of various CRISPR/Cas-based techniques applicable to the detection of, defense against, and treatment of viral infections. These techniques include viral diagnostics, the development of antiviral vaccines, B cell engineering for antibody production, viral activation/interference, and epigenetic modifications. Furthermore, this review delves into the challenges and bioethical considerations associated with use of the CRISPR/Cas system. With the continuous evolution of technology, the CRISPR/Cas system holds considerable promise for addressing both existing and unforeseen biological threats. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.