Over the last decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes at an unprecedented scale. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g., irrigation, artificial dams, and water diversion) and at various scales (from a watershed to the globe). During the early 1990s, awareness of the potential water scarcity led to the first detailed global water resource assessments. Shortly thereafter, in order to analyse the human perturbation on terrestrial water resources, the first generation of large-scale hydrological models (LHMs) was produced. However, at this early stage few models considered the interaction between terrestrial water fluxes and human activities, including water use and reservoir regulation, and even fewer models distinguished water use from surface water and groundwater resources. Since the early 2000s, a growing number of LHMs are incorporating human impacts on hydrological cycle, yet human representations in hydrological models remain challenging. In this paper we provide a synthesis of progress in the development and application of human impact modeling in LHMs. We highlight a number of key challenges and discuss possible improvements in order to better represent the human-water interface in hydrological models.