During the Holocene (last ~11,700 years), societies have continuously modified the landscape of the Mediterranean Basin through changes in land-use, exerting extraordinary pressures onto the environment and adding variability to the climate. Despite its importance to current land management, knowledge of how past land-use practices have impacted the regional climate of the Basin remains largely in the scientific sphere. Thereby, this work aims to inform non-scientific actors and practitioners about the environmental effects of past land-use changes on the hydrologic cycle of the Mediterranean Basin. For this purpose we: i) summarize fundamental observed interactions between land-use change and the environment, identified through a semi-systematic review of 23 scientific case-studies from around the Basin; ii) reflect on the consequences to the Mediterranean environment (atmosphere, biosphere, lithosphere, and hydrosphere) in a synthesized and integrated way; iii) argue the need for taking into account the impact of local land-use practices from a regional-scale perspective; iv) highlight the importance of recognizing historical factors, such as past land-use changes, for developing protective strategies in the rural areas of the Basin. With this work, we provide a synthesized and more integrated understanding of the effects of past and local land-use changes in the regional Mediterranean environment, assisting to bridge the gap between scientific findings, Mediterranean watersheds stakeholders, and regional policy-makers.