The Brazilian Cerrado, one of the most threatened biomes of our planet, illustrates the challenges and opportunities of reconciling economic development with conservation of land and water ecosystems. Here, we assess the state of the art of and present new information on the impacts of agricultural expansion, dams, and water use, and make recommendations for basin management, conservation, and restoration of water‐related Cerrado ecosystems and rivers. The conservation of the Cerrado requires not only the preservation of remnants of its vegetation but also the ability to keep the hydro‐geomorphological and ecological functionality of its rivers, particularly the Araguaia River, the last large well preserved and unregulated system. If business as usual continues, the Cerrado riverine ecosystems may never rebound.