The Laurentian Great Lakes of North America provide valuable ecosystem services, including fisheries, to the surrounding population. Given the prevalence of other anthropogenic stressors that have historically affected the fisheries of the Great Lakes (e.g., eutrophication, invasive species, overfishing), climate change is often viewed as a long-term stressor and, subsequently, may not always be prioritized by managers and researchers. However, climate change has the potential to negatively affect fish and fisheries in the Great Lakes through its influence on habitat. In this paper, we (1) summarize projected changes in climate and fish habitat in the Great Lakes; (2) summarize fish responses to climate change in the Great Lakes; (3) describe key interactions between climate change and other stressors relevant to Great Lakes fish, and (4) summarize how climate change can be incorporated into fisheries management. In general, fish habitat is projected to be characterized by warmer temperatures throughout the water column, less ice cover, longer periods of stratification, and more frequent and widespread periods of bottom hypoxia in productive areas of the Great Lakes. Based solely on thermal habitat, fish populations theoretically could experience prolonged optimal growth environment within a changing climate, however, models that assess physical habitat influences at specific life stages convey a more complex picture. Looking at specific interactions with other stressors, climate change may exacerbate the negative impacts of both eutrophication and invasive species for fish habitat in the Great Lakes. Although expanding monitoring and research to consider climate change interactions with currently studied stressors, may offer managers the best opportunity to keep the valuable Great Lakes fisheries sustainable, this expansion is globally applicable for large lake ecosystem dealing with multiple stressors in the face of continued human-driven changes.