ABSTRACT Emerging infectious diseases are a major threat to global aquaculture production and are projected to increase in frequency due to anthropogenic stressors and climate change. Our ability to screen the global aquatic ‘infectome’ is dramatically improving through unbiased metatranscriptomic (i.e., total RNA) sequencing. Despite recent advances in molecular diagnostics and next‐generation sequencing, outbreak investigation in aquaculture often encounters limitations due to the targeted nature of conventional techniques, which may only capture a small portion of the diverse array of disease‐causing agents present in nature, sometimes requiring years to resolve. Here, we propose that unbiased metatranscriptomic sequencing serves as a cost‐effective and powerful technique for characterising pathogens during disease outbreaks and in surveillance programmes. In doing so, we offer a diagnostic framework to mitigate infectious disease threats to global aquaculture. We emphasise the importance of combining rapid metatranscriptomics with traditional techniques for a holistic examination of the causes of unknown aetiologies in aquatic animals, and how it can be used to examine host responses in parallel with pathogen discovery. We suggest that the integration of metatranscriptomics into aquaculture will require upskilling, proficiency testing, user‐friendly bioinformatic tools and open data sharing. Furthermore, it is essential to establish a reporting framework—with analytical guidelines—that ensures the protection of animal industries while safeguarding trade interests.