Central Asian water resources largely depend on melt water generated in the Pamir and Tien Shan mountain ranges. To estimate future water availability in this region, it is necessary to use climate projections to estimate the future glacier extent and volume. In this study, we evaluate the impact of uncertainty in climate change projections on the future glacier extent in the Amu and Syr Darya river basins. To this end we use the latest climate change projections generated for the upcoming IPCC report (CMIP5) and, for comparison, projections used in the fourth IPCC assessment (CMIP3). With these projections we force a regionalized glacier mass balance model, and estimate changes in the basins' glacier extent as a function of the glacier size distribution in the basins and projected temperature and precipitation. This glacier mass balance model is specifically developed for implementation in large scale hydrological models, where the spatial resolution does not allow for simulating individual glaciers and data scarcity is an issue. Although the CMIP5 ensemble results in greater regional warming than the CMIP3 ensemble and the range in projections for temperature as well as precipitation is wider for the CMIP5 than for the CMIP3, the spread in projections of future glacier extent in Central Asia is similar for both ensembles. This is because differences in temperature rise are small during periods of maximum melt (July–September) while differences in precipitation change are small during the period of maximum accumulation (October–February). However, the model uncertainty due to parameter uncertainty is high, and has roughly the same importance as uncertainty in the climate projections. Uncertainty about the size of the decline in glacier extent remains large, making estimates of future Central Asian glacier evolution and downstream water availability uncertain.