Vietnam ranks third in global aquaculture production (FAO, 2012) with a total of 3.2 million tons, of which fish contributed with more than 2.2 million tons (Fisheries Directorate, 2014). Most is produced in the Mekong delta region where the dominating freshwater species are air-breathing and include catfish (Pangasianodon hypophthalmus and Pangasius bocourti), snake head (Channa striata), and swamp eel (Monopterus albus); with mud skipper (Pseudapocryptes elongatus) in the brackishwater. On a global scale, the production of air-breathing species now represent 8% of the global cultured fish production and therefore exceed the total global production of salmonids. Air-breathing probably evolved in response to hypoxia and these fish are well adapted to conditions considered poor for water breathing fish. The separation of ion regulatory and oxygen uptake functions at branchial surfaces seems also to have conveyed enhanced tolerance to common toxins and the freshwater species of the Mekong delta all seem tolerant to brackish water. Data on these issues will be presented and research needs for the continued development of air-breathing fish culture highlighted.