Size and conspicuousness do not track together. The perentie is the fourth largest lizard in the world after the Komodo dragon, the crocodile monitor and the Asian water monitor, but its range is the stony interior of Australia, far from most human settlement, and its habits are wary. Approached, it typically runs, sometimes rearing to a bipedal stance to look over cover before doing so.
It shelters in burrows it digs itself and in rock crevices, emerging to forage widely. Prey spans insects, other reptiles including goannas and snakes, birds, eggs, small mammals such as rabbits, and carrion. Like other monitors it uses a forked tongue and the vomeronasal organ to track scent trails.
The perentie holds a place in the traditions of several Aboriginal peoples, as food and as a totemic animal. It is not considered threatened, though data on population trends across such a vast and thinly surveyed range are limited, which is a general caveat for arid-zone Australian reptiles rather than a specific concern about this species.