Assessments of the regional impacts of human-induced climate change on a wide range of social and environmental systems are fundamental for determining the appropriate policy responses to climate change(1-3). Yet regional-scale impact assessments are fraught with difficulties, such as the uncertainties of regional climate-change prediction(4), the specification of appropriate environmental-response models(5), and the interpretation of impact results in the context of future socio-economic and technological change(6). The effects of such confounding factors on estimates of climate-change impacts have only been poorly explored(3-7). Here we use results from recent global climate simulations(8) and two environmental response models(9,10) to consider systematically the effects of natural climate variability (30-year timescales) and future climate-change uncertainties on river runoff and agricultural potential in Europe. We find that, for some regions, the impacts of human-induced climate change by 2050 will be undetectable relative to those due to natural multi-decadal climate variability. If misleading assessments of-and inappropriate adaptation strategies to-climate-change impacts are to be avoided, future studies should consider the impacts of natural multidecadal climate variability alongside those of human-induced climate change.