Black footed ferrets have largely declined due to the loss of prey resulting from an extensive campaign to eradicate prairie dogs, mainly through poisoning. Canine distemper is fatal for black-footed ferrets and it has decimated many populations and is a serious threat to reintroduced populations. Conversion of land to agricultural use has led to fragmentation of Black-footed Ferret habitat. As ferrets live at low densities, a breeding population is spread over a large area, fragmentation reduces the populations ability to reproduce.
The IUCN considers [Mustela nigripes] as "Extincnt in the Wild". CITES lists the species as "Appendix 1".