Desalination is expanding exponentially across the world. Yet, there is little research on the economic, institutional, and social dimensions of desalination, as well as on policy-relevant lessons for managing the risks and opportunities from this technology, especially in low- and middle-income countries. This perspective article proposes a broad research agenda anchored in five key themes – energy and materials, institutions and regulations, social dynamics and perception, strategic planning, and financial sustainability – and grounded in the principles of open science to help steer the sustainable and equitable roll-out of desalination globally.