No species in North America today more powerfully represents the United States than the plains bison (popularly called “buffalo”); preserving Bison bison bison Linnaeus, and its genetic integrity, is important to the nation. This paper first examines the bison's prehistory, migrations to North America, relationship with North American Native American cultures, and events leading to the nineteenth century near-extinction. It then discusses early conservation successes, including the work of individuals and organizations that made this possible. This paper focuses on mainly the prospects for bison protection today in the face of strong challenges such as bison-cattle (Bos Taurus Bojanus) interbreeding and the threat of bison genomic extinction. This work is being carried out by bison protection organizations and a Department of the Interior (DOI) bison working group. Their goals include finding and establishing connected habitats wherein buffalo can roam and migrate as they did historically across broad ranges. Maintaining genetic integrity and creating safe habitats for bison herds can lead to long-term viability.