The rate of forest destruction has accelerated sharply in Brazilian Amazonia, but there are also vital conservation opportunities with the ongoing designation of important new protected areas. In a timely paper, Carlos Peres argues that an extensive network of mega-reserves, operationally defined as those exceeding 1 million ha in area, is needed to ensure the long-term persistence of Amazonian species and ecological processes. Although such protected areas might seem excessively large to some, disparate lines of evidence suggest that mega-reserves are vital for the future of Amazonian biodiversity.