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Biodiversity is being lost globally, at devastating rates. The 15th Conference of the Parties to the Convention on Biological Diversity will finalise a global biodiversity conservation framework for 2020-2050. The negotiations must result in ambitious yet workable targets that protect and restore nature, while equitably and sustainably sharing nature’s contributions to people. This Collection of research and opinion articles from Nature Ecology & Evolution and Nature Sustainability speak to the goal-setting process and the scientific underpinnings of effective biodiversity conservation.