The animals are now fair game after U.S. Congress agreed to lift federal safeguards the western states of Montana and Idaho.
There are about 1,200 wolves in the wild and their removal from the list means they are now state controlled and allows for licensed hunting.
Fair game: Grey wolves are going to become the first animals to be taken off the endangered species list
Ranchers, who have seen the population of the wolf growing in the Northern Rockies, have said they are glad that this has happened because of the threat they pose to their herds.
Cattle producers, hunters and state game wardens say that wolf packs in some places are going unchecked as they prey on livestock and other animals such as elk.
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However pro-animal experts say it could be a slippery slope to taking more animals off the list.
Senator Jon Tester, who put forward the motion, said: 'Right now, Montana's wolf population is out of balance, and this provision will get us back on the responsible path with statement management.'
People against the decision say they fear it opens a 'Pandora's box' that will allow for more animals to be taken off the list
Similar plans were turned down in 2009 by federal judges after an application by the U.S. Fish and Wildlife Service saying that it would violate the Endangered Species Act.
Wildlife expert Matt Kirby said: 'Congress has never before made a species-specific decision. It opens up a Pandora's box where you could have politicians cherry-picking inconvenient species.'
The Obama administration has sought to quell the dispute by persuading wildlife advocates to embrace the management plans of Montana and Idaho as adequate to keep wolf populations at healthy levels now that they exceed recovery targets.
On Saturday, Molloy rejected the plan again after it was presented as a negotiated settlement between the federal government and 10 conservation groups. Several environmental organizations continue to oppose it.
Once abundant across most of North America, grey wolves were hunted, trapped and poisoned to near extinction in much of the continental United States by the 1930s under a government-sponsored eradication program.
Decades later, biologists recognized that wolves had an essential role to play in mountain ecosystems as a predator. Listed as endangered in 1974, the animals have made a comeback in the region around Yellowstone National Park since the government reintroduced them there in the mid-1990s.
The language now before Congress would override Molloy and put the 2009 plan back into place.
A number of animals have been removed from the U.S. endangered species list over the years through a process of scientific review established under federal law.
But this legislation would mark the first time an animal has been removed by Congress from the endangered list.