This paper assesses the hydrological response to scenarios of climate change in the Okavango River catchment in Southern Africa. Climate scenarios are constructed representing different changes in global mean temperature from an ensemble of 7 climate models assessed in the IPCC AR4. The results show a substantial change in mean flow associated with a global warming of 2°C. However, there is considerable uncertainty in the sign and magnitude of the projected changes between different climate models, implying that the ensemble mean is not an appropriate generalised indicator of impact. The uncertainty in response between different climate model patterns is 10 considerably greater than the range due to uncertainty in hydrological model parameterisation. There is also a clear need to evaluate the physical mechanisms associated with the model projected changes in this region. The implications for water resource management policy are considered.