Humans and tigers are the main enemies of gray wolves. Although wolves often encounter opposition from prey or from other animals looking to steal their kill, only humans and tigers seek out nearby wolves with intent to kill.

Wolves are often misperceived as dangerous, bloodthirsty creatures, which led to their widespread eradication as humanity expanded across the Old and New Worlds. People feared that gray wolves would eat their livestock or harm their families. Very few records exist of wolves injuring humans. Wolves prefer to keep to themselves and their territories, eating large hoofed animals and small mammals, such as elk and rabbits, in the wild rather than livestock near humans. Gray wolves drive away other predatory animals that attempt to steal their kills or compete with them when food is scarce.