The title track was borne out of a poem Mellencamp's friend George Green wrote as a eulogy he delivered at the grave site upon the death of his grandfather. “He had no intention of using it as a song,” Mellencamp said in a 2008 interview with the Bloomington Herald Times. “He had me read it and I said, ‘These are the best lyrics you ever wrote.’ He said, ‘They’re not lyrics’ and I said ‘I can make them lyrics.’ I took it and kind of cut it up and wrote the chorus.”
The album is dedicated to band member John Cascella, who died unexpectedly about halfway through production of the album.
Entertainment Weekly gave the record an "A" rating, stating: "John Mellencamp's last album was more or less straight-ahead rock, but there's something dark and unshaven about his new one, 'Human Wheels.' Oddball instruments — pennywhistles, mandolins — pop up like disordered wraiths over gritty drum tracks that sound like they were recorded in a cluttered cellar. Mellencamp himself mutters and snarls in a voice of tangled complexity, worrying his way through songs about trouble."