Aquaculture is the production, under controlled conditions, of freshwater or saltwater aquatic organisms for human consumption and non-food use. Worldwide aquaculture has increased remarkably in the last decades and now accounts for approximately half of the total production of aquatic animals. The expansion of aquaculture has several environmental impacts due to the production of feed ingredients, the disposal of aquafarm effluents, disease transmission, and the dispersal of invasive species. Among the aquaculture technologies, land-based recirculating aquaculture systems (RASs) have a much greater impact due to the massive use of energy, water, and other resources. Aquaponics is a system that couples fish production in RAS with soilless plant cultivation. Aquaponic systems can produce both plant and animal food with a much greater use efficiency of land and water and a minor environmental impact compared to conventional food production systems such as in-land aquafarming greenhouse horticulture. In this chapter, along with a brief description of hydroponic technologies and RASs, several issues concerning the application of aquaponics on a commercial scale are discussed, such as the selection of fish and crop species; the development of salt-water aquaponics systems; the system monitoring; the protection of fish and crop; animal health and welfare; economic and environmental sustainability. Finally, the concept of self-sufficient integrated multi-trophic aquaponic system is briefly introduced.