The purpose of this Global Perspective is to discuss the ecological impacts of desalination intakes in coastal ecosystems and to highlight current global policies and trends. Suggestions are provided based on regulatory needs and knowledge gaps required to better evaluate the ecological risks of such facilities. Desalination has emerged as an increasingly popular response to the intensifying global water demands and shortages in recent decades. As of 2019, the number of operational desalination facilities was estimated at nearly 16,000, with 48% located in the Middle East and North Africa. Current trends indicate that new and planned facilities are overwhelmingly membrane-based desalination facilities, specifically seawater reverse osmosis (SWRO) facilities. Large-scale SWRO facilities draw millions of gallons each day from source waters, potentially leading to the impingement, entrapment, and entrainment of massive numbers of aquatic organisms, with potential implications for community structure and function via multiple indirect mechanisms. Despite these potentially devastating environmental impacts, there remains a paucity of enforceable regulations pertaining to intake structure siting, design, and operation of large desalination facilities worldwide.