Climate change has the potential to compromise the sustainability of natural resources in Mediterranean climatic systems, such that short-term reactive responses will increasingly be insufficient to ensure effective management. There is a simultaneous need for both the clear articulation of the vulnerabilities of specific management systems to climate risk, and the development of appropriate short- and long-term strategic planning responses that anticipate environmental change or allow for sustainable adaptive management in response to trends in resource condition. Governments are developing climate change adaptation policy frameworks, but without the recognition of the importance of responding strategically, regional stakeholders will struggle to manage future climate risk. In a partnership between the South Australian Government, the Adelaide and Mt Lofty Ranges Natural Resource Management Board and the regional community, a range of available research approaches to support regional climate change adaptation decision-making, were applied and critically examined, including: scenario modelling; applied and participatory Geographical Information Systems modelling; environmental risk analysis; and participatory action learning. As managers apply ideas for adaptation within their own biophysical and socio-cultural contexts, there would be both successes and failures, but a learning orientation to societal change will enable improvements over time. A base-line target for regional responses to climate change is the ownership of the issue by stakeholders, which leads to an acceptance that effective actions to adapt are now both possible and vitally important. Beyond such baseline knowledge, the research suggests that there is a range of tools from the social and physical sciences available to guide adaptation decision-making.