One of the major public health concerns today is the contamination of water bodies and food sources with antibiotic-resistant bacteria (ARB). The widespread and often indiscriminate use of antibiotics in aquaculture, spanning various stages of production, has significantly contributed to the evolution of ARB. As these resistant pathogens continue to spread, there is growing concern that we could face a microbial apocalypse, where common infections become untreatable due to the lack of effective antibiotics. To mitigate the growing threat of ARB, it is imperative that we focus on several key strategies. This chapter discusses the development of new antibiotics and alternative therapies that minimize the reliance on antibiotics, such as promoting better hygiene, biosecurity measures, bacteriophage therapy, or alternative feed additives and the use of probiotics or other natural treatments to conventional antibiotics in aquaculture and other agricultural sectors.