The advent of CRISPR-Cas9 technology offers a groundbreaking approach to managing microbial infections in aquatic environments. The chapter explores the application of CRISPR-Cas9 for the therapeutic management of these infections, emphasizing its potential to revolutionize aquaculture and ecological health. CRISPR-Cas9 enables precise genetic modifications, allowing for targeted disruption of pathogenic microorganisms and enhancement of host resistance. Key applications include the development of disease-resistant aquaculture species, enhanced phage therapy targeting bacterial pathogens, and microbiome engineering to promote beneficial microbial communities. These strategies promise to reduce reliance on antibiotics and chemical treatments, mitigating environmental and resistance-related concerns. However, the deployment of CRISPR-Cas9 must navigate significant challenges, including technical delivery methods, potential off-target effects, and ecological risks associated with genetically edited organisms. Ethical considerations and public acceptance are also critical, necessitating transparent stakeholder engagement and robust regulatory frameworks. The future success of CRISPR-Cas9 in this domain depends on addressing these challenges while harnessing its transformative potential for sustainable aquatic health management. This chapter underscores the importance of ongoing research and responsible innovation to fully realize the benefits of CRISPR-Cas9 in combating aquatic microbial infections.