Increasing rates of habitat loss and human occupation are creating demands for optimum strategies that maximize conservation efforts, despite the lack of detailed data required for implementation. Broad scale biogeographical data may furnish initial guidelines for conservation planning in a hierarchical framework for establishing conservation priorities and helping guide future research programmes. This approach may be critical in regions for which few detailed data on diversity, abundance and distribution are available, such as in the Cerrado biome of central Brazil. We used a macroecological approach, based on the extent of occurrence of 127 species of terrestrial vertebrates endemic to the Cerrado, to design a regional network of potential areas that represent all species at least once. The final network has a total of 24 regions widely distributed throughout the biome. We also evaluated these regions in terms of their human occupation by adding a cost for each cell based on 23 variables expressing variation in agricultural, demographic and cattle-ranching patterns on the Cerrado. Our analyses showed that conservation efforts should be concentrated in the south and south-east of the biome. This macroecological approach can provide broad guidelines for conservation and define the focus for more local and realistic conservation efforts.