The central Ebro Basin is an exceptional region for studying karstification through time and under different environmental conditions, as sinkholes have been developing since the Early Pleistocene. Knowledge of active sinkholes is complemented with research on paleosinkholes and contemporary deposits. Sedimentological, mineralogical, geomorphological and structural approaches permit interpretation of the natural environmental conditions that favored karst in the past and the main genetic mechanisms involved. The sedimentary features of Pleistocene terraces indicate that they were deposited by a gravel braided fluvial system characterized by higher water and sediment availability than today, probably related to meltwater flows coming from glaciated source areas, mainly in the Pyrenees. Genesis of paleosinkholes was mainly linked to this high water supply. Some of them acted as small lakes where fine sediments are exceptionally well conserved to give clues about environmental conditions. The neoformation of palygorskite and sepiolite suggests arid to semiarid climatic conditions, in agreement with the idea of cold glacial episodes. During Pleistocene times, development of sinkholes was influenced by tectonics. Currently, the genesis and evolution of numerous sinkholes are also influenced by water supplies from human activities such as irrigation or urbanization, sharply changing the nearly steady state exhibited in the past.