In a context of international scrutiny, important efforts are being made to preserve Brazil’s tropical forests. Meanwhile, the destruction of its Cerrado biome advances with increasing leaps but little controversy. Yet the damaging changes threaten life-supporting natural resources and ecosystem services that are vital for the majority of Brazilians, as well as for the continued viability of agriculture. This ancient region of considerable geological and cultural significance encapsulates all of the major environmental challenges to sustainability, and begs new responses from science and society. Fresh policies are needed to promote and integrate the importance of this biome for the nation. These include implementing systematic monitoring systems and improving the management of established ones, minimizing new clearing. Degraded areas must be restored to comply with existing Brazilian environmental laws and international commitments related to climate change, biodiversity conservation, and sustainable development. Addressing the threats to this critically important yet neglected biome requires attention to structural governance problems, including improved education and involvement of stakeholders in key decision making about the region, as well as historically informed reexamination of the country’s economic development path.