There is an increasing need for paleoclimate records from continental settings to better understand the climatic changes during critical periods such as the Pliocene and Early Pleistocene. Present data indicates a transition from a warmer than present-day climate to a substantially different cooler climate. This study reviews the oxygen and carbon isotope compositions of mammalian tooth enamel for the Pliocene and Early Pleistocene of South and Central Europe to reconstruct the spatial distribution and temporal changes of the vegetation and oxygen isotope composition of precipitation (δ18Oppt). In addition to a literature review, this study adds new stable isotope measurements for this period. All δ13C values indicate C3 ecosystems and reflect major changes in the water use efficiency and/or in the prevailing humidity. The reconstructed major floral types range from woodland to woodland ‒ mesic grassland in all of the investigated regions. The carbon isotope compositions of fossil mammal teeth demonstrate that the spatial distribution of vegetation was broadly similar to those of the present-day for the Early/Late Pliocene – Early Pleistocene, with the most “closed” vegetation in Central and Northern Italy, while open mesic grassland vegetation covers can be reconstructed for the Iberian Peninsula, Massif Central region (Central France) and the Carpathian Basin. The calculated δ18Oppt values give a negative temporal shift of about 1–1.5‰ from the Early Pliocene to Late Pliocene – Early Pleistocene in three regions (Iberian Peninsula, Central Italy, Carpathian Basin), potentially representing a 1.5–3.0 °C decrease in mean annual temperatures (MAT) over time. In the Massif Central region and the Carpathian Basin, the δ18Oppt values are almost the same for the Late Pliocene and Early Pleistocene, while in Northern Italy the values decreased over that period. The δ18Oppt values are in the range of present-day δ18Oppt values over the Early Pliocene and somewhat lower than present-day values for the Late Pliocene - Early Pleistocene in most of the regions. Because most other proxies indicate warmer than present-day climate for the Early Pliocene and similar to present-day climate for the Early Pleistocene, the δ18Oppt values are generally lower than expected, which can be partially explained by local effects.