We examined the potential impacts of climate variability and change on human health as part of a congressionally mandated study of climate change in the United States. Our author team, comprising experts from academia, government, and the private sector, was selected by the federal interagency U.S. Global Change Research Program, and this report stems from our first 18 months of work. For this assessment we used a set of assumptions and/or projections of future climates developed for all participants in the National Assessment of the Potential Consequences of Climate Variability and Change. We identified five categories of health outcomes that are most likely to be affected by climate change because they are associated with weather and/or climate variables: temperature-related morbidity and mortality; health effects of extreme weather events (storms, tornadoes, hurricanes, and precipitation extremes); air-pollution-related health effects; water- and foodborne diseases; and vector- and rodent-borne diseases. We concluded that the levels of uncertainty preclude any definitive statement on the direction of potential future change for each of these health outcomes, although we developed some hypotheses. Although we mainly addressed adverse health outcomes, we identified some positive health outcomes, notably reduced cold-weather mortality, which has not been extensively examined. We found that at present most of the U.S. population is protected against adverse health outcomes associated with weather and/or climate, although certain demographic and geographic populations are at increased risk. We concluded that vigilance in the maintenance and improvement of public health systems and their responsiveness to changing climate conditions and to identified vulnerable subpopulations should help to protect the U.S. population from any adverse health outcomes of projected climate change.