Koyukon Elders of Alaska’s Interior observe that “cold weather is growing old” and recent warming is contributing to a world out of balance. Alaska is among the most rapidly warming places globally, with the Interior experiencing the most pronounced warming statewide, and with significant regional-scale ecosystem services disruptions affecting subsistence hunting and harvest success. Vulnerability of individuals, households, and communities to climate change is exacerbated by rising energy costs and a regulatory system that constrains the adaptive flexibility needed to cope with impacts on livelihoods. Socioeconomic and cultural change notwithstanding, the well-being of rural native communities is still dependent on access and ability to harvest wild foods, with moose the example explored in this study. In the fall of 2004, there was a convergence during the moose hunting season of warming climatic conditions with social, political, and ecological events and conditions that affected the ability of subsistence hunters in the region to successfully harvest moose. By combining indigenous observations and understanding of climate and western social/natural sciences, this study examines the complex, multi-scaled interaction of climate change and subsistence livelihoods, with the goal of understanding vulnerability and adaptive capacity in the Koyukuk-Middle Yukon (KMY) region.