This commentary explores the relationships between land, knowledge, and health for Indigenous peoples. Indigenous knowledge is fundamentally relational, linked to the land, language and the intergenerational transmission of songs, ceremonies, protocols, and ways of life. Colonialism violently disrupted relational ways, criminalizing cultural practices, restricting freedom of movement, forcing relocation, removing children from families, dismantling relational worldviews, and marginalizing Indigenous lives. However, Indigenous peoples have never been passive in the face of colonialism. Now more than ever, Indigenous knowledge in three critical areas-food and water security, climate change, and health-is needed for self-determination and collective survival in a rapidly changing world.