Accelerating environmental change is perhaps the greatest challenge for natural resource management; successful strategies need to be effective for decades to come. Our objective is to identify opportunities that new environmental conditions may provide for conservation, restoration, and resource use in a globally recognized biodiversity hotspot in southwestern Australia. We describe a variety of changes to key taxonomic groups and system-scale characteristics as a consequence of environmental change (climate and land use), and outline strategies for conserving and restoring important ecological and agricultural characteristics. Opportunities for conservation and economic adaptation are substantial because of gradients in rainfall, temperature, and land use, extensive areas of remnant native vegetation, the ability to reduce and ameliorate areas affected by secondary salinization, and the existence of large national parks and an extensive network of nature reserves. Opportunities presented by the predicted environmental changes encompass agricultural as well as natural ecosystems. These may include expansion of aquaculture, transformation of agricultural systems to adapt to drier autumns and winters, and potential increases in spring and summer rain, carbon-offset plantings, and improving the network of conservation reserves. A central management dilemma is whether restoration/preservation efforts should have a commercial or biodiversity focus, and how they could be integrated. Although the grand challenge is conserving, protecting, restoring, and managing for a future environment, one that balances economic, social, and environmental values, the ultimate goal is to establish a regional culture that values the unique regional environment and balances the utilization of natural resources against protecting remaining natural ecosystems.