Decades of study have attempted to define a generalized environmental-heterogeneity-biodiversity (EH-BD) relationship, with the traditional MacArthurian niche-based hypothesis remaining as the dominant reference point; i.e., increasing heterogeneity promotes biodiversity by increasing resource opportunities. However, studies have frequently reported negative or nonsignificant relationships. In a vast majority of them, environmental heterogeneity was defined along a gradient of increasing randomness, toward complete disorder. A new conceptual framework could help to reconcile the array of observed relationships. Using an extensive literature review, we test a conceptual framework proposing that the direction of environmental-heterogeneity-biodiversity relationships is contingent on the level of human footprint to which an ecosystem is subjected (the anthropocline). The results reveal that highly modified and seminatural ecosystems are characterized by a dominance of positive and negative EH-BD relationships, respectively, whereas natural ecosystems show mixed responses. Out of this novel framework arises the revised perspective that natural ecosystems are typified, not by maximal or minimal, but by intermediate levels of environmental heterogeneity.