The Mekong is one of the world's great rivers. It has the greatest mean annual flow in the world for a river basin of comparable size. The flow regime, with very distinct wet and dry seasons, supports a rich biodiversity and the world's largest freshwater fishery. Given that at the present time the hydrological regime of the Mekong remains in its natural state, the accelerating pace of water resources development will induce hydrological change. The natural productivity of the system is therefore potentially jeopardized. This paper reports the findings of simulation studies of the potential hydrological impacts of water resource development scenarios over future planning horizons. In the Definite Future scenario (next 5 years), the seasonal redistribution of water by on-going hydropower development will increase the dry season flow by 40–60% in the upper portion of the basin and by 20–30% in the Mekong Delta. The Foreseeable Future scenario (next 20 years) and Long-Term Future scenario (next 50 years) will result in relatively small changes to the flow regime as further increases in dry season reservoir releases will be offset by planned increases in irrigation and other consumptive water demands. All scenarios were predicted to reduce the average wet season flows by 4–14%, flow reversal to the Tonle Sap Lake by 7–16%, flooded areas by 5–8% and salinity intrusion areas in the Viet Nam Delta by 15–17%. Predicted changes in Definite Future scenario will be irreversible, necessitating improved coordination between the LMB countries and cooperation with China in order to manage the risks and maximize the regional benefits. The scenario assessments highlighted the areas where research is necessary to mitigate and manage impacts in order to ensure the reasonable and equitable use of the Mekong basin's water resources. Copyright © 2013 John Wiley & Sons, Ltd.