A wide range of resource managers, community planners, and other stakeholders are increasingly asking for information regarding how climate change will affect South Carolina’s freshwater and coastal resources. They are interested in using this information for decisions related to infrastructure design, water system planning, vulnerability assessments, and ecosystem management. While climate change data, projections, and related information are also becoming increasingly available, many uncertainties around future climate change and its potential impacts often hinder its application. Furthermore it is often not available in a format or at a scale that is easily translated to local- and regional resource management decisions. This article highlights decision-maker questions about climate change in the Carolinas, approaches to using global climate change information, and opportunities to bridge the gap that often exists between scientific research and applications. We find that integration of future climate scenarios with water resources issues succeeds when robust links exist between climate variables and system response, and when scenarios from observed or simulated climate data are representative, plausible, and consistent. In general, there is no one “best” model that depicts future climate conditions, nor can climate science provide accurate predictions for specific locations and impacts. However, climate change projections can be used in conjunction with a variety of other tools and resources, such as vulnerability assessments and historical climate observations, to inform planning processes. Improved understanding of the system of concern, the linkages to climate, and the most important variables can help decision makers and researchers alike to develop the most relevant and informative analyses for climate-related questions. Ongoing engagement, as well as a willingness to experiment and share lessons learned, between and across the resource management and science communities will help to advance the climate change dialogue in the Carolinas and enhance the production and use of climate change information.