In December 2010, the Office of Biological and Environmental Research of the U.S. Department of Energy in conjunction with the U.S. Global Change Research Program convened a workshop in Arlington, Virginia to address questions and issues regarding the use of mathematical models for the National Climate Assessment (NCA). The workshop also addressed the complex issues that arise when data and models are applied at multiple spatial and temporal scales, an inherent requirement of a national climate assessment. An Interagency National Climate Assessment (INCA) Task Force provided guidance regarding purpose, scope, and objectives of the workshop. The results of the workshop in turn offer guidance not only for the National Climate Assessment but also more generally for future research in the use of models for these tasks. The workshop included plenary-session presentations and panels as well as breakout group discussions. Presentations and discussions covered both global and regional climate models and linkages of these models to enable regional analyses or downscaling of variables constrained by global model results. Participants reviewed potential use of carbon cycle and other biogeochemical cycling models as well as a range of models for analyzing the impacts of climate change on various sectors and within different regions. Integrated assessment models that relate climate change to human factors were discussed, as were various options for coupling models (used to assess climate change impacts) to either data on human activities or models of various human systems. Participants offered significant insights about the use of models within the overall NCA structure of linked sectors and regions. A number of workshop findings and recommendations apply to the development of a longer-term, sustained Assessment process.