It is set in the same fictional town of Pine Cove, California, as his first novel, Practical Demonkeeping, and also brings back some of the same characters.

Pine Cove suffers a major crisis when the town psychiatrist, Val Riordan — who has been haphazardly issuing prescriptions instead of dealing with the real mental problems of her patients — suffers a sudden bout of guilt and substitutes all of her patients' anti-depressants with placebos.

In addition to its ability to change form, the beast exudes a pheromone that inspires uncontrollable lust among the residents of Pine Cove and also lures some of them as prey.

Meanwhile, Theophilus Crowe, the town constable, investigates a strange suicide, the activities of his corrupt boss, and his adversely affected marijuana habit.

James Sallis praised Lust Lizard, saying that Moore's novel provides "[like] all the best comic writing, something beyond jokes, caricature, spinning plates and crazy-tilt towers, something intangible that vanishes whenever we try to look directly at it: some sense, perhaps, that we're still able to rescue from the ever-increasing detritus of our culture a decent, simple humanity.