Conservation priority-setting schemes have not yet combined geographic priorities with a framework that can guide the allocation of funds among alternate conservation actions that address specific threats. We develop such a framework, and apply it to 17 of the world's 39 Mediterranean ecoregions. This framework offers an improvement over approaches that only focus on land purchase or species richness and do not account for threats. We discover that one could protect many more plant and vertebrate species by investing in a sequence of conservation actions targeted towards specific threats, such as invasive species control, land acquisition, and off-reserve management, than by relying solely on acquiring land for protected areas. Applying this new framework will ensure investment in actions that provide the most cost-effective outcomes for biodiversity conservation. This will help to minimise the misallocation of scarce conservation resources.