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The Mediterranean region is both a global biodiversity hot spot and one of the biomes most strongly affected by human activities. Ecologists and land managers are increasingly required to advise on threats to biodiversity under foreseeable climate change. We used expert surveys to evaluate current understanding and uncertainties regarding climate change impacts on biodiversity in terrestrial, inland freshwater, and marine ecosystems of Israel. Finally, we propose a response strategy toward minimizing these changes. The surveys and the published literature indicated that the main climate change impacts in Israel include ongoing deterioration of freshwater habitats, decline of shrubland and woodland areas, and increased frequency and severity of forest fires. For the Mediterranean Sea, the surveys predict further introduction and establishment of invasive species from the Red Sea, accelerated erosion of coastal rocky habitat, and collapse of coastal rocky platforms. In the Gulf of Aqaba, Red Sea, corals may be resilient to foreseen climate change due to their high tolerance for rising water temperatures. Despite these predictions, science-based knowledge regarding the contribution of management toward minimizing climate change impacts on biodiversity is still lacking. Habitat loss, degradation, and fragmentation are presently the primary and immediate threats to natural ecosystems in Israel. Protection of natural ecosystems, including local refugia, must be intensified to maintain existing biodiversity under pressure from mounting urban development and climate change. This protection policy should include ecological corridors to minimize the consequences of fragmentation of existing natural habitats for species survival. A longer-term strategy should mandate connectivity across environmental and climatic gradients to maintain natural resilience by allowing reorganization of natural ecosystems facing climate change.