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Expansion of the global protected-area network has been proposed as a strategy to address threats from accelerating climate change and species extinction. A key step in increasing the effectiveness of such expansion is understanding how novel threats to biodiversity from climate change alter concepts such as rewilding, which have underpinned many proposals for large interconnected reserves. We reviewed potential challenges that climate change poses to rewilding and found that the conservation value of large protected areas persists under climate change. Nevertheless, more attention should be given to protection of microrefugia, macrorefugia, complete environmental gradients, and areas that connect current and future suitable climates and to maintaining ecosystem processes and stabilizing feedbacks via conservation strategies that are resilient to uncertainty regarding climate trends. Because a major element of the threat from climate change stems from its novel geographic patterns, we examined, as an example, the implications for climate-adaptation planning of latitudinal, longitudinal (continental to maritime), and elevational gradients in climate-change exposure across the Yellowstone-to-Yukon region, the locus of an iconic conservation proposal initially designed to conserve wide-ranging carnivore species. In addition to a continued emphasis on conserving intact landscapes, restoration of degraded low-elevation areas within the region is needed to capture sites important for landscape-level climate resilience. Extreme climate exposure projected for boreal North America suggests the need for ambitious goals for expansion of the protected-area network there to include refugia created by topography and ecological features, such as peatlands, whose conservation can also reduce emissions from carbon stored in soil. Qualitative understanding of underlying reserve design rules and the geography of climate-change exposure can strengthen the outcomes of inclusive regional planning processes that identify specific sites for protection.