Uranium occurrence and development has left a legacy of long-lived health effects for many Native Americans and Alaska Natives in the United States. Some Native American communities have been impacted by processing and development while others are living with naturally occurring sources of uranium. The uranium production peak spanned from approximately 1948 to the 1980s. Thousands of mines, mainly on the Colorado Plateau, were developed in the western U.S. during the uranium boom. Many of these mines were abandoned and have not been reclaimed. Native Americans in the Colorado Plateau area including the Navajo, Southern Ute, Ute Mountain, Hopi, Zuni, Laguna, Acoma, and several other Pueblo nations, with their intimate knowledge of the land, often led miners to uranium resources during this exploration boom. As a result of the mining activity many Indian Nations residing near areas of mining or milling have had and continue to have their health compromised. This short review aims to rekindle the public awareness of the plight of Native American communities living with the legacy of uranium procurement, including mining, milling, down winders, nuclear weapon development and long term nuclear waste storage.