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Anthropogenic pressures are causing the widespread loss of wildlife species and populations, with adverse consequences for ecosystem functioning. This phenomenon has been widely but inconsistently referred to as defaunation. A cohesive, quantitative framework for defining and evaluating defaunation is necessary for advancing biodiversity conservation. Likening defaunation to deforestation, we propose an operational framework for defaunation that defines it and related terms, situates defaunation relative to intact communities and faunal degradation, and encourages quantitative, ecologically reasonable, and equitable measurements. We distinguish between defaunation, the conversion of an ecosystem from having wild animals to not having wild animals, and faunal degradation, the process of losing animals or species from an animal community. The quantification of context-relevant defaunation boundaries or baselines is necessary to compare faunal communities over space and time. Situating a faunal community on the degradation curve can promote Global Biodiversity Framework targets, advancing the 2050 Vision for Biodiversity.