What do people mean when they say a river is “alive,” or that “water is life”? Native Americans have been asking and answering these questions for more than 10,000 years. This is especially true for the Cherokee people. In river valleys across Southern Appalachia, untold generations of Cherokees nurtured special relationships with some of America's most important headwaters. How did they do it? This lecture offers some answers. It reveals how Cherokees developed stories, historical insights, and scientific knowledge that nurtured webs of life that pulse from the mountaintops to distant seas. Dr. Gregory D. Smithers is a professor of American history at Virginia Commonwealth University whose research and teaching focuses on the histories of Indigenous people and African Americans from the eighteenth century to the present. His work is particularly interested in the rich history of the Cherokee people, Indigenous history from the Mountain South to California and the Southwest Pacific, environmental history, and the history of race, gender, and sexuality. His books include *Native Southerners: Indigenous History from Origins to Removal* and *The Water Carriers: A Journey through Cherokee History and the Secret Life of Rivers*. *The content and opinions expressed in these presentations are solely those of the speaker and not necessarily of the Virginia Museum of History & Culture.*