Landscape-scale approaches to conservation stem largely from the classic ideas of reserve design: encouraging bigger and more sites, enhancing connectivity among sites, and improving habitat quality. Trade-offs are imposed between these four strategies by the limited resources and opportunities available for conservation programmes, including the establishment and management of protected areas, and wildlife-friendly farming and forestry. Although debate regarding trade-offs between the size, number, connectivity and quality of protected areas was prevalent in the 1970-1990s, the implications of the same trade-offs for ongoing conservation responses to threats from accelerating environmental change have rarely been addressed. Here, we reassess the implications of reserve design theory for landscape-scale conservation, and present a blueprint to help practitioners to prioritise among the four strategies. We consider the new perspectives placed on landscape-scale conservation programmes by twenty-first century pressures including climate change, invasive species and the need to marry food security with biodiversity conservation. A framework of the situations under which available theory and evidence recommend that each of the four strategies be prioritized is provided, seeking to increase the clarity required for urgent conservation decision-making.