The principal threat to the forests of the Madrean Pine-Oak Woodlands is logging. The exploitation of pines and, to a lesser extent, oaks for timber has increased, in some areas becoming indiscriminate. Additionally, many non-timber forest products are also being used unsustainably. For example the vascular epiphyte (Tillandsia usneoides) is extracted for Christmas ornamental purposes in Mexico, and a large variety of mushrooms in pine-oak forests, including species in the genera AmanitaLeccinumRussula, and Boletus, are collected for culinary use.

Fire is partly a natural process in this ecosystem, but intentional burning to foster regeneration of fresh sprouts for livestock grazing or to clear land for agricultural purposes is altering habitats throughout the region. In southern Arizona, 90 years of fire suppression by federal and state agencies and modification of fuels by grazing and other causes, has led to conifer forests at higher elevations changing from open-grown ponderosa pine (Pinus ponderosa) to dense stands of mixed conifers.

The fragmented nature of the hotspot makes it difficult to arrive at a reliable estimate of the amount of original vegetation remaining intact. Pine-oak forests once covered about 21 percent of Mexico, but these remaining forests now cover no more than about 8 percent. Such estimates, however, fail to account for stands that have been impacted by fire and overgrazing, and so it seems reasonable to expect that no more than about 20 percent of the hotspot's original vegetation can be considered pristine.