Maintaining spatial–temporal connectivity for conservation is necessary to allow the persistence of ecological processes and the biodiversity they sustain. However, conservation practice in human-modified environments can also benefit from prescribed disconnection through the implementation of barriers. Barriers, such as fences or dams, and buffer zones can be a cost-effective way of addressing threats caused by a globally connected world, such as the propagation of invasive species and diseases, creating refuge areas for native biodiversity and helping reduce economic losses caused by native wildlife or invasive species. Despite the global attention that disconnection has received, no clear framework exists to guide the allocation of barriers for conservation management. Here we propose that the implementation of barriers for conservation should be systematically planned, considering ecological trade-offs for multiple species (easing threats vs. interruption of ecosystem processes) and socio-economic cost–benefits (implementation cost vs. reduced human–wildlife conflicts), rather than using ad-hoc opportunistic criteria or accommodating conservation needs for individual species. Such a systematic approach is necessary to ensure both socially acceptable and ecologically effective use of disconnections as a conservation tool and ideally planned across different realms so co-benefits or trade-offs can be accounted for. However, any implementation of disconnection for conservation should be cautiously considered if uncertainty in effectiveness of the barrier and ecological impacts to other species are high. We also suggest the need for improved approaches to monitoring to learn from previous successes and failures. Our recommendations should guide the systematic evaluation and allocation of barriers to help enhance the value of this conservation tool in the face of increasing propagation of threats worldwide. However, new tools and collaborative frameworks across different realms are needed to help stakeholders make better informed decision.