A membrane material that can concurrently provide commercially acceptable levels of water permeability, high salt rejection, and of sufficient stability to withstand mechanical and chemical stresses seems to be necessary to guarantee the energy and environmental sustainability of desalination systems and other membrane separation processes. Recent developments in desalination have shown that bio-inspired membranes are moving steadily in this direction. Sustainable desalination via aquaporin-based bio-inspired membranes is elucidated in this paper in terms of recent commercialization exploitation and progress towards real operations. Current large-scale applications, viable opportunities, remaining challenges and sustainability of operations, in terms of comparison with established technologies, are discussed in this paper. The major drawback of aquaporin-based membranes, which has been highlighted repeatedly in recent studies, is the stability of the membranes during real operations. This review is focused on recent solutions provided by scientists towards the mitigation of these problems and commercialization of aquaporin-based membranes.