It is nearly three decades since the world recognized the need for a global multilateral treaty aiming to address accelerating biodiversity loss. However, biodiversity continues to decline at a concerning rate. Drawing on lessons from the implementation of the current strategic plan of the Convention on Biological Diversity and the 2010 Aichi Targets, we highlight three interlinked core areas, which require attention and improvement in the development of the post-2020 Biodiversity Framework under the Convention on Biological Diversity. They are: (1) developing robust theories of change which define agreed, adaptive plans for achieving targets; (2) using models to evaluate assumptions and effectiveness of different plans and targets; and (3) identifying the common but differentiated responsibilities of different actors/states/countries within these plans. We demonstrate how future multilateral agreements must not focus only on what needs to be done but also on how it should be done, using measurable steps, which make sense at the scales at which biodiversity change happens.