Economic development in the Mekong region has brought with it considerable environmental change, with more to follow. The river has already been highly modified by a plethora of perturbations, but hydropower is the most transparent in the public eye. However, other forces are in action not least disconnection of the flood plains for agriculture, aggregate extraction and growing urbanization. These have all impacted on the fish and fisheries and the capacity delivery aquatic food products from the system, but the system has to date remained largely resilient, or has it? This paper reviews the outputs of Mekong River Commission’s Council Study and Vietnamesae Government Mekong Delta Study to tease out the role of hydropower development in the widespread changes being observed in the system and how fisheries have responded. The methodologies behind the studies and the future prospects of the river and how the fisheries may be impacted will be presented. Finally, opportunities that may help to mitigate future development scenarios, especially with respect to hydropower development will be explored.