The global proliferation of intellectual property rights (IPRs), most recently through the World Trade Organization’s Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement, poses a grave threat for Indigenous knowledge systems. There is an increasing amount of “piracy” of Indigenous knowledge, whereby corporations and scientists from rich countries are claiming proprietary rights over knowledge that has belonged to cultures and people for hundreds of years. From the hoodia cactus and the Mexican yellow bean, to the use of neem and turmeric in India, IPRs have been inappropriately utilized to promote growth for the rich while hindering development and perpetuating poverty within many Indigenous knowledge-holding communities. The separation of humans from culture, culture from ecology, and ecology from economics has caused severe ecological exploitation and subsequent degradation. This article frames the current debate at the intersection of IPRs and Indigenous knowledge, proposing several alternatives that embrace the purposes of modernity’s use of knowledge ownership mechanisms while promoting ecological sustainability through the protection and valorization of Indigenous knowledge.