On the run to nowhere, Charlie Reese searches for death, but his brush with the supernatural has left its mark, sealing his fate. To remind him, the Apothecary sends the reluctant Coyote Moon, the last Prince of the Animawalkers, to protect him, even if it is from himself.

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Charlie's destructive path leads him away from the depressed streets of Chicago to the Great American Desert. All the while, Coyote Moon attempts to steer him into rebuilding his will to live. Charlie resists the temptations until he is reunited with a familiar face, one that rekindles his ingrained sense of duty. Forced to confront his inner demons, as well as those of Hades, Charlie will either have to fight or break his most sacred vow.