Some authors have proposed that M. nigripes might be conspecific with Steppe Polecat M. eversmanii (Wozencraft 2005), but this is not a treatment generally followed.

Black-footed Ferret is categorised as Endangered because of its very small and restricted populations. As of early 2015, there are about 295 wild born mature individuals distributed among several re-established populations. Of these, 206 are in self-sustaining free-living populations. Of the 24 current sites where this species has been reintroduced, few have viable populations. The number of breeding adults declined by about 40% from 2008 to 2015 (approximately two generations).  Although formerly widespread in central North America, the species declined through the 20th century to near extinction by the late 1970s, primarily as a result of prairie-dog Cynomys control actions and sylvatic plague; by 1987, it was considered Extinct in the Wild. The current populations result from massive efforts to reintroduce captive animals back to the wild. It was reintroduced by the United States Fish and Wildlife Service into eight western states of the USA, one state in Mexico, and one province in Canada from 1991 to 2009. Populations in Mexico and Canada are now considered extirpated. At present, it is considered self-sustaining at only four locations (two in South Dakota, one in Arizona and one in Wyoming). Even with augmentation, wild Black-footed Ferret populations remain small, fragmented, and intensively managed.

Historically, Black-footed Ferret was found throughout the Great Plains, mountain basins, and semiarid grasslands of west-central North America, from southern Canada to northern Mexico wherever its prey, prairie-dogs Cynomys, were located (Hillman and Clark 1980). This species was extirpated from most of its former range mainly as a result of prairie-dog control programmes and sylvatic plague - an exotic disease which was introduced to the wild population. Today, it occurs in the wild as 17-22 reintroduction efforts, only four of which are self-sustaining. These four are in South Dakota, Wyoming and Arizona (all USA), and have a combined range exceeding 500 km². There are four populations of limited success in Kansas, New Mexico, South Dakota and Utah, USA; six populations of recent initiation in Arizona, Colorado and  Montana (all USA); two populations in Canada and Mexico which are now again extirpated; and six declining or extirpated populations in Colorado, Montana, New Mexico and South Dakota (all USA).

It has been recorded from 500 to 3,100 m asl.

There are no known non-introduced wild Black-footed Ferret populations (Nowak 2005). This species nearly went extinct in the late 1980s and existing populations are the success of massive efforts to reintroduce this species back to its native habitat. Captive breeding has been successful. Several hundred individuals exist in six ex situ breeding facilities and as of early 2015, approximately 500 wild-living (released or wild born) individuals exist in populations in several US states and Mexico.

Reintroduction began in 1991 with the release of one group into the Shirley Basin of Wyoming. Since 1987, over 8,000 kits have been produced through captive breeding and since 1991, over 3,900 Ferrets have been released at 24 sites. When possible, populations are sampled and counted at least once a year as part of a management and recovery protocol. At the spring count of 2008 there were approximately 500 breeding adults in the wild, fewer than 250 of which had been born in the wild. The estimated number of breeding adults rose to 448 in 2009, but had declined to 274 in 2012, and was similar in 2015, at 295. The overall approximate population decline from 2008 to 2015 was about 40%. Of these, 206 mature individuals occur in self-sustaining free-living populations. These minimum population estimates occur in the spring. Maximum population estimates occur in the fall and include young of the year.

Black-footed Ferret is limited to open habitat, the same habitat used by prairie-dogs Cynomys: grasslands, steppe and shrub steppe. It depends largely on prairie-dogs, preying on them and using their burrows for shelter and denning (Hillman and Clark 1980). Ferret habitat selection at fine scales is dependent on density of prairie-dog burrow openings (Eads et al. 2011, 2013). It has been estimated that about 40-60 hectares of prairie-dog colony are needed to support one Black-footed Ferret. Ayers et al. (2014) found that Black-footed Ferrets successfully recruited offspring with prairie-dog densities of at least 12 individuals/ha in ferret core areas. Biggins et al. (1993, 2006) provided information on evaluating areas as potential Black-footed Ferret habitat; factors include size of prairie-dog complex, prairie-dog population density, spatial arrangement of prairie-dog colonies, potential for disease in prairie-dogs and in ferrets, potential for prairie-dog expansion, abundance of predators, future resource conflicts and ownership stability, and public and landowner attitudes.

The extreme dependence of Black-footed Ferret on prairie-dogs Cynomys made it especially vulnerable to extinction because its prey were persecuted as agricultural pests during most of the 20th century (Biggins and Godbey 2003). Populations declined rapidly as a result of widespread extermination of prairie-dogs and the spread of canine distemper and plague Yersinia pestis (Biggins and Godbey 1995, Biggins et al. 1998). Plague is an exotic disease that did not exist in North America prior to 1900. It can affect Black-footed Ferret directly via infection and subsequent mortality, and indirectly through mortality of prairie-dogs and resultant dramatic declines in the Ferret's prey base  (e.g., Eads and Biggins 2015). Multiple techniques and approaches are currently being developed and tested to reduce direct and indirect threats caused by plague.

Populations of Black-footed Ferrets declined throughout the 20th century to near extinction by the late 1970s (Biggins and Schroeder 1988). A small remnant population (around 100 animals or fewer; Schreiber et al. 1989) was discovered in 1981 near Meeteetse, in northwestern Wyoming, but that population was decimated by canine distemper and plague in 1985 (Forrest et al. 1988).

Another major threat is the loss of habitat by conversion of grasslands to agricultural uses; the remaining habitat is now fragmented by great expanses of cropland and human development. In addition, the gene diversity of the current captive population as determined by pedigree analysis is estimated to be about 86% of that which was present in the population's founders (Garelle et al. 2014). This decrease in genetic diversity and concomitant increase in inbreeding may decrease fitness through inbreeding depression, including immune system dysfunction and reduced reproductive success (Bronson et al. 2007).

This species is not used.

The Black-footed Ferret captive breeding programme was initiated in October 1985 by the Wyoming Game and Fish Department in cooperation with the United States Fish and Wildlife Service. Eighteen Black-footed Ferrets were captured between 1985 and 1987 from the last-known population, in Wyoming, to start a captive breeding population (Miller et al. 1996), with the ultimate goal of reintroduction.

Because of relatedness among many of the 18 Ferrets captured, genetic contributions equate to no more than seven founder equivalents. As of 2008, there are six institutions (one federal facility and five zoos) participating in the propagation programme under the supervision of the United States Fish and Wildlife Service. Beginning in 1985, more than 8,000 Black-footed Ferrets have been born in captivity, with 323 kits weaned in 2014. Beginning in 1991, Ferrets have been reintroduced at sites in eight Western U.S. states (Montana, South Dakota, Wyoming, Colorado, Utah, Arizona, Kansas and New Mexico), one site in Mexico (Bard 2002, Bronson et al. 2007) and one site in Canada. In 2014 alone, 202 kits were released at nine separate reintroduction sites..

The species is listed on CITES Appendix I and is listed under the U.S. Endangered Species Act.