The desert tortoise is very sensitive to human disturbances, and this has led to the decimation of many of its populations throughout the desert southwest. Increased urban development in the deserts of California and other states have fragmented and reduced suitable habitat. Certain fatal diseases appear to be spreading among tortoise populations. Poaching, the use of off-highway vehicles within tortoise habitat and crushing by automobiles have also continued to threaten tortoise populations.

Ravens cause significant levels of juvenile tortoise predation in some areas of the Mojave Desert with more prevalence of human disturbances.

Climate change [1] projections suggest that difficult times may be ahead for the desert tortoise as heat and droughts expand over the region. Like all reptiles, tortoises have minimal ability to self-regulate their internal temperature, and thus must retreat to the shade of vegetation or their burrows once the air temperature reaches above 91 degrees Fahrenheit, in order to keep their body temperatures out of the danger zone. Droughts also force the tortoises to spend more time in their underground burrows to minimize water loss; thus both heat and drought decreasing the amount of time they are able to spend feeding. Droughts limit the availability of nutritious forage for the tortoises.

Females also lay fewer eggs during drought years. Furthermore, the sex of the young turtles is determined by the soil temperature during incubation. Temperatures above 88.7 degrees Fahrenheit produce female tortoises, so prolonged high temperatures could skew the sex distribution of future generations. Extremely high soil temperatures (above 95 degrees) are lethal to the developing young.