Climate change-related risks are place-specific and path-dependent. Accordingly, location is an important determinant of hazardous exposure, and certain places will bear more risk than others. This article reviews the major environmental exposures associated with risky places in the U.S., including coastal regions, islands, the desert Southwest, vectorborne and zoonotic disease border regions, cities, and the U.S. Arctic (Alaska), with emphasis on exposures and vulnerable populations of concern. In addition to these hotspots, this study considers the ways in which the concept of place--the sense of human relationship with particular environments--will play a key role in motivating, developing, and deploying an effective public health response. In considering the importance of place, we highlight the concepts of community resilience and risk management, key aspects of a robust response to climate change in public health and other sectors.