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Recognizing the importance for adaptation to the climate change impact on water resources, the IAEA has developed guidelines and recommendations on the selection and application of isotope-enabled hydrological models, which can enhance the predictive power of modelling catchment systems for hydrological forecasting, as well as support more realistic water flux and storage simulations of the natural environment. This publication is designed to support modellers and water managers interested in isotope-enabled modelling. It was developed by isotope hydrologists, data network and modelling specialists from different countries, what shared a unique experience on model selection, modelling objectives, data collection and modelling procedure. Examples of their isotope modelling applications have been provided to give context to the guidelines and recommendations made by this publication, where these examples highlight the versatility of isotopes across a range of different environmental and climate settings. Lessons learned from application of isotope-enabled modelling techniques in each of the diverse climate and water settings are discussed.