Sustainable aquaculture production is made possible by ameliorating stress, mitigating microbial infections, and preventing water quality deterioration. Diseases are one of the major concerns in intensive aquaculture systems. Frequent application of chemotherapeutics such as antimicrobials can exacerbate antibiotic resistance and will hamper environmental sustainability. Rational aquaculture advocates alternative strategies for improving the growth and immunity of cultured organisms. This includes the application of probiotics, prebiotics, immunostimulants, vaccines, phage and photodynamic therapy, and various herbal products. Among these, probiotics are found to have multiple applications in aquaculture. The application of probiotics in aquaculture improves the health of cultured organisms and the water quality of the culture system. Probiotics administered through feed (gut probiotics) are proven to promote digestion and absorption of the host organism. Furthermore, they contribute to the increased synthesis of essential nutrients such as vitamins, fatty acids, and carbohydrates, thereby augmenting the immune system of the host. Probiotics play a role in managing aquatic pathogens by generating inhibitory compounds, competing for nutrients and energy resources, contending for mucosal surface colonization, and disrupting quorum sensing. Besides, the water quality can also be improved by the administration of probiotics directly (pond probiotics) as bioaugmentors in the culture system. Microbes such as Bacillus sp., Lactobacillus sp., Lactococcus sp., Carnobacterium sp., Bifidobacterium sp., Streptomyces, Saccharomyces cerevisiae, and so on are the dominant groups reported as probiotics in aquaculture. The application of prebiotics such as inulin, oligofructose, galactooligosaccharides, mannan oligosaccharides, and so on along with probiotics is known as synbiotics and improves the activity and survival of probiotic bacteria. This chapter summarizes the diversity of probiotic and prebiotic compounds, their selection strategies, mode of action, method of administration, and individual and combined application of probiotics and prebiotics as synbiotics in aquaculture. The article also addresses the limitations, challenges, safety concerns, and prospects of probiotics and synbiotics for augmenting sustainable and eco-friendly aquaculture production.