In a context of climate, environmental, ecological and socio-economical changes, understanding and predicting the response of hydrological systems on regional to global spatial scales, and on infra-seasonal to multidecadal time-scales, are major topics that must be considered to tackle the challenge of water resource management sustainability. In this context, a number of strongly-linked key issues need to be addressed by the scientific community, including: (i) identifying climate drivers of hydrological variations, (ii) understanding the multi-frequency characteristics of hydroclimate variability, including evolution of extremes (meteorological/hydrological event scale to long-term natural/internal climate- or anthropogenic-driven variations and trends), (iii) assessing the influence of local- to regional-scale basin properties on hydrological system response to climate variability and change, (iv) identifying the evolving contribution of anthropogenic water use in observed hydrological variations. Based on pan-European collaborations, activities of the EURO-FRIEND “Large-scale variations in hydrological characteristics” group aim at generating new findings to improve our understanding of hydrological systems behavior sensu lato (i.e. surface and sub-surface) on large spatial and temporal scales (i.e continental – multidecadal). Through selected examples, this contribution emphasizes recent research developments in characterizing and modeling of climate-hydrology linkages at different temporal and spatial scales, as well as recent insights on climate-hydrology scaling characteristics (i.e. long-term persistence, dependance of processes, of hydrological behaviors, of large-scale climate/hydrology linkages on time-/spatial scales), long-term hydrometeorological reconstructions, and large-scale hydrological model refinement taking into account spatial heterogeneity of watershed physical characteristics.