The intensification of productivity in aquaculture has been accompanied by an increasing demand for environmentally friendly production. Ecological impacts including emergence of a large variety of pathogens and the development of resistant bacterial strains are growing. These impacts are in part due to the indiscriminate use of chemotherapeutic agents as a result of poor management practices in production cycles. There is a rapidly increasing literature pointing to the success of immunostimulants, plant products, and oral vaccines that can enhance growth; stimulate the innate, cellular, and/or humoral immune response; and control the number of pathogens that lead to fish diseases. It has been documented that supplemented diets may play an important role in improving immunity, health status, feed efficiency, nutrition, breeding, and growth performance of the host organism. Prebiotics are indigestible components in a diet that are metabolized by specific microorganisms and they prove helpful for the growth and health of the host by selectively stimulating the growth of and/or activating the metabolism of one or a limited number of health-promoting bacteria in the intestinal tract. Probiotics are microorganisms or their products that exhibit health benefits to the host through actively inhibiting the colonization of potential pathogens in the digestive tract by antibiosis or by competition for nutrients and/or space, alteration of microbial metabolism, and/or the stimulation of host immunity. They also may stimulate appetite and improve nutrition by the production of vitamins, detoxification of compounds in the diet, and breakdown of indigestible components. There is accumulating evidence that probiotics are effective at inhibiting a wide range of fish pathogens, but the reasons for the inhibitions are not completely understood and evidence is often contradictory. However, the modes of action of these compounds are still considered to be hypotheses that need to be widely investigated. Dietary applications of prebiotics and probiotics may be combined to achieve a common objective in sustainable fish production. This chapter highlights the understanding of prebiotics, probiotics, and their combination, which provides pointers to the future of aquaculture.