The design of Biosphere Reserves (BR) poses an interesting problem for systematic planning. It entails a spatially explicitly compromise between economic, social, cultural and biodiversity protection objectives, in a sustainable development context. The global network of Biosphere Reserves includes 563 sites in 110 countries. Currently the spatial configuration of BRs follows a nested scheme, where different land use regimes are assigned to zones in an ad hoc fashion, which complicates the evaluation of their effectiveness. So far in the literature, have not been designed to achieve quantitative objectives, which could limit their value for sustainable development. Using the newly developed version of the software MARXAN © , we solve part of this problem enabling BRs to reach predefined set of spatially explicit quantitative targets, while minimizing the reserves' overall costs (i.e. opportunity, implementation, land value, etc.). Our case study is the Pantanal Biosphere Reserve (PBR), in Brazil. According to our results the PBR could substantially improve its effectiveness if a systematic review of its objectives and goals is performed. Rearrangements of all zones proved to be necessary. Core zones for example, composed of IUCN categories I to IV, increased from its current 1.5% of the BR area to 18.5% to reach all objectives. The absence of quantitative guidelines from UNESCO for the configuration of BRs has limited their effectiveness. Our quantitative systematic approach provided the first insights into potential requirements for zone partitioning, prescribing 22 ± 5% to be allocated in core zones, 22 ± 3% in buffer zones, and 33 ± 4% in transition zones. The most useful outcome, however, was the flexibility the software offered to reach multiple objectives simultaneously.