[3][4] The Gila monster is sluggish in nature, so it is not generally dangerous and very rarely poses a real threat to humans.

They appear strong in their body structure with a stout snout, massive head, and "little"-appearing eyes, which can be protected by a nictitating membrane.

[3][4] The evolutionary history of the Helodermatidae may be traced back to the Cretaceous period (145 to 166 million years ago), when Gobiderma pulchrum and Estesia mongolensis were present.

Fragments of osteoderms from the Gila monster have been found in Late Pleistocene (10,000 to 8,000 years ago) deposits near Las Vegas, Nevada.

[11] The scales of the head, back, and tail contain little pearl-shaped bones (osteoderms) similar to those found in the beaded lizards from further south.

[3] They inhabit scrubland, succulent desert, and oak woodland, seeking shelter in burrows, thickets, and under rocks in locations with a favorable microclimate and adequate humidity.

[18] One study investigating a population of Gila monsters in southwestern Utah noted that the lizard's activity peaked from late April to mid June.

[13] Gila monsters are slow sprinters, but they have relatively high endurance and maximal aerobic capacity (VO2 max) compared to other lizards.

Among adaptations to a dry environment is a slow metabolism, allowing them to use less than half the amount of energy expected for lizards of their size.

[21] The Gila monster's diet consists of a variety of food items – small mammals (such as young rabbits, hares, mice, ground squirrels, and other rodents), small birds, snakes, lizards, frogs, insects, other invertebrates, carrion, and the eggs of birds, lizards, snakes, and tortoises.

The strong, two-ended tipped tongue, which is pigmented in black-blue colors,[12] picks up scent molecules to be transferred to the opening of the Jacobson organ around the middle of the upper mouth cavern.

Prey may be crushed to death if large, or eaten alive, most of the time head first, and helped down by muscular contractions and neck flexing.

After food has been swallowed, the Gila monster may immediately resume tongue flicking and search behavior for identifying more prey such as eggs or young in nests.

In the Old West, the pioneers believed a number of myths about the Gila monster, including that the lizard had foul or toxic breath and that its bite was fatal.

It is supposed that this is one way in which the monster catches the insects and small animals which form a part of its food supply – the foul gas overcoming them."

When Scientific American ran another ill-founded report on the lizard's ability to kill people, he wrote in reply and described his own studies and personal experience.

Symptoms of the bite include excruciating pain, edema, and weakness associated with a rapid drop in blood pressure.

YouTuber Coyote Peterson described the bite as "like hot lava coursing through your veins" and claimed it was "the worst pain [he] had ever experienced".

[37] More than a dozen peptides and other substances have been isolated from the Gila monster's venom, including hyaluronidase, serotonin, phospholipase A2, and several kallikrein-like glycoproteins responsible for the pain and edema caused by a bite, without producing a compartment syndrome.

[41] The constituents of H. suspectum venom that have received the most attention from researchers are the bioactive peptides, including helodermin, helospectin, exendin-3, and exendin-4.

[42] Exendin-4, which is specific for H. suspectum, has formed the basis of a class of medications for the treatment of type 2 diabetes and obesity/metabolic syndrome, known as the GLP-1 receptor agonists.

The effectiveness is because the lizard protein is 53% identical to glucagon-like peptide-1 analog (GLP-1), a hormone released from the human digestive tract that helps to regulate insulin and glucagon.

Using a sophisticated injection formula with sustained release of the drug, the lizard protein remains effective much longer than the human hormone.

Discussions of the exact egg development and hatching cycle of the Gila monster came to an abrupt and unexpected end on October 28, 2016, when a backhoe was digging at the outer walls of a house in a suburb of northern Tucson.

In summer, Gila monsters gradually spend less time on the surface to avoid the hottest part of the season; occasionally, they may be active at night.

[3] Although the Gila monster has a low metabolism and one of the lowest lizard sprint speeds, it has one of the highest aerobic scope values (the increase in oxygen consumption from rest to maximum metabolic exertion) among lizards, allowing it to engage in intense aerobic activity for a sustained period of time.

A more successful strategy would be, for example, if the new "settlers" were offered intensive education about this species (e.g., limited toxicity, lifestyle) with the aim of tolerating the reptile or even being proud of having this unique "roommate" in one's own neighborhood.

[49] In the last two decades, experienced breeders have shared their knowledge and expertise to give advice to other herpetologists on overcoming the difficulties in Heloderma reproduction under human care.

In Brock Brower's 1971 novel The Late Great Creature, fictional horror movie star Simon Moro is presented as famous for playing the reptilian werewolf-like Gila Man.

The 2011 animated film Rango featured a Gila monster as an Old West outlaw named Bad Bill, voiced by Ray Winstone.