The black-footed ferret, a member of the weasel family, is one of the most endangered mammals in North America. It ranged from the Rocky Mountains eastward throughout the Great Plains. Dramatic declines of the black-tailed prairie dog, white-tailed prairie dog, and Gunnison's prairie dog have taken a brutal toll on the ferret, which is dependent on prairie dogs for both food and habitat. Prairie dogs make up 90% of the ferret's diet, although they will also eat mice, ground squirrels, rabbits, and other animals. Ferrets also rely on prairie dog burrows for shelter. Ferrets are preyed on by coyotes, raptors, badgers, and other carnivores; prairie dog burrows offer ferrets and their young protection from predation.

Ferrets historically occupied more than 100 million acres of western grasslands but are now reduced to a handful of reintroduction sites in the wild. While programs to breed ferrets in captivity have been successful, efforts to reintroduce captive-bred ferrets into the wild have frequently failed when prairie dog populations crash due to sylvatic plague and other factors. Ferrets themselves can die from plague, and are also susceptible to canine distemper and predation by other carnivores.

Healthy ferret populations require very large prairie dog complexes. If efforts to recover white-tailed, black-tailed, and Gunnison's prairie dogs are successful, we may yet recover the black-footed ferret as well. Center for Native Ecosystems has monitored the black-footed ferret release program in northwestern Colorado, watchdogging the Bureau of Land Management to ensure that the released ferrets are adequately protected.