Land-use/land-cover change is the most important factor in causing biodiversity loss. The Mediterranean region has been affected by antropic disturbance for thousands of years, and is, nowadays, one of the most significantly altered hotspots in the world. However, in the last years a significant increase in forest cover has been measured. These new patterns are independent from planned conservation strategies and appear to have a substantial impact on landscapes and biodiversity. We used three land-use/land-cover maps (from 1960 to 2000) covering the Italian peninsula to analyze the pattern of land-use/land-cover change. We measured an increase in forests, especially in mountains, an increase in artificial areas, especially in coastal zones, and a decrease in pastures. Intensively cultivated areas showed a limited decrease while extensively cultivated ones showed a marked decrease. In the same period mammal and bird species followed a similar pattern, with forest birds, ungulates and carnivores increasing, and typically Mediterranean species decreasing. We suggest that our results may provide important information, which could be useful for conservation planning in the entire Mediterranean hotspot. We suggest that an increasing conservation effort should be made to protect the Mediterranean-type forests and scrublands, as well as traditional agricultural practices. Moreover, future conservation efforts should consider the broad socio-political and ecological processes that are most likely to occur across the whole hotspot, especially along coastal areas, and the network of protected areas should be functionally integrated in a conservation strategy that includes the human-dominated landscape.