The GLOBIO3 model has been developed to assess human-induced changes in biodiversity, in the past, present, and future at regional and global scales. The model is built on simple cause–effect relationships between environmental drivers and biodiversity impacts, based on state-of-the-art knowledge. The mean abundance of original species relative to their abundance in undisturbed ecosystems (MSA) is used as the indicator for biodiversity. Changes in drivers are derived from the IMAGE 2.4 model. Drivers considered are land-cover change, land-use intensity, fragmentation, climate change, atmospheric nitrogen deposition, and infrastructure development. GLOBIO3 addresses (i) the impacts of environmental drivers on MSA and their relative importance; (ii) expected trends under various future scenarios; and (iii) the likely effects of various policy response options. GLOBIO3 has been used successfully in several integrated regional and global assessments. Three different global-scale policy options have been evaluated on their potential to reduce MSA loss. These options are: climate-change mitigation through expanded use of bio-energy, an increase in plantation forestry, and an increase in protected areas. We conclude that MSA loss is likely to continue during the coming decades. Plantation forestry may help to reduce the rate of loss, whereas climate-change mitigation through the extensive use of bioenergy crops will, in fact, increase this rate of loss. The protection of 20% of all large ecosystems leads to a small reduction in the rate of loss, provided that protection is effective and that currently degraded protected areas are restored.