Some landscapes cannot be understood without references to the kinds, degrees, and history of human-caused modifications to the Earth's surface. The tropical latitudes of the Andes represent one such place, with agricultural land-use systems appearing in the Early Holocene. Current land use includes both intensive and extensive grazing and crop- or tree-based agricultural systems found across virtually the entire range of possible elevations and humidity regimes. Biodiversity found in or adjacent to such humanized landscapes will have been altered in abundance, composition, and distribution in relation to the resiliency of the native species to harvest, land cover modifications, and other deliberate or inadvertent human land uses. In addition, the geometries of land cover, resulting from differences among the shapes, sizes, connectivities, and physical structures of the patches, corridors, and matrices that compose landscape mosaics, will constrain biodiversity, often in predictable ways. This article proposes a conceptual model that implies that the continued persistence of native species may depend as much on the shifting of Andean landscape mosaics as on species characteristics themselves. Furthermore, mountains such as the Andes display long gradients of environmental conditions that alter in relation to latitude, soil moisture, aspect, and elevation. Global environmental change will shift these, especially temperature and humidity regimes along elevational gradients, causing changes outside the historical range of variation for some species. Both land-use systems and conservation efforts will need to respond spatially to these shifts in the future, at both landscape and regional scales.