This chapter presents an overview of the impact of Cartesian science, and the mechanistic thinking that has accompanied it, on the health of Indigenous people. The chapter identifies the challenges faced by Indigenous people in many countries that has resulted from the clash of philosophies as Western countries, influenced by Cartesian science, have sought to colonize Indigenous people. These challenges to traditional Indigenous values and Indigenous ways of life and the separation of Indigenous people from country have led to an ever-escalating negative impact on Indigenous health and well-being.