The projection of robust regional climate changes over the next 50 years presents a considerable challenge for the current generation of climate models. Water cycle changes are particularly difficult to model in this area because major uncertainties exist in the representation of processes such as large-scale and convective rainfall and their feedback with surface conditions. We present climate model projections and uncertainties in water availability indicators (precipitation, run-off and drought index) for the 1961-1990 and 2021-2050 periods. Ensembles from two global climate models (GCMs) and one regional climate model (RCM) are used to examine different elements of uncertainty. Although all three ensembles capture the general distribution of observed annual precipitation across the Middle East, the RCM is consistently wetter than observations, especially over the mountainous areas. All future projections show decreasing precipitation (ensemble median between -5 and -25%) in coastal Turkey and parts of Lebanon, Syria and Israel and consistent run-off and drought index changes. The Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) GCM ensemble exhibits drying across the north of the region, whereas the Met Office Hadley Centre work Quantifying Uncertainties in Model ProjectionsAtmospheric (QUMP-A) GCM and RCM ensembles show slight drying in the north and significant wetting in the south. RCM projections also show greater sensitivity (both wetter and drier) and a wider uncertainty range than QUMP-A. The nature of these uncertainties suggests that both large-scale circulation patterns, which influence region-wide drying/wetting patterns, and regional-scale processes, which affect localized water availability, are important sources of uncertainty in these projections. To reduce large uncertainties in water availability projections, it is suggested that efforts would be well placed to focus on the understanding and modelling of both large-scale processes and their teleconnections with Middle East climate and localized processes involved in orographic precipitation.