In this paper, the term multi-purpose water infrastructure (MPWI) encompasses all man-made water systems, including dams, dykes, reservoirs and associated irrigation canals and water supply networks, which may be used for more than one purpose (for economic, social and environmental activities). While MPWI plays a significant role in the socio-economic development and ensuring water, food and energy security of many countries (not least in water-stressed Central Asia), many MPWI projects face various challenges. These including unsustainability of business models for financing, operation and maintenance, lower-than-expected performance or the emergence of unforeseen risks and negative externalities. This paper explores the complexity in designing, financing, regulating and managing MPWI projects, with the objective to inform policy and decision-making. It attempts to identify key issues related to managing MPWI, lessons learned from international experience and possible solutions to the challenges. It examines several principles, approaches and instruments to enhance the sustainability of MPWI, drawing on international experience. Finally, the paper identifies knowledge and experience gaps, needs for further research and possible areas of future work.