The collection touches on subjects ranging from family, race, violence, and celebrity to music, writing, and coming of age in Mississippi.

While it was originally called On Parole, Laymon said that "while my relationship with paragraphs, chapters, and dead authors was getting more intimate, I was getting worse at being human...later that night, I could not sleep, and for the first time in my life, I wrote the sentence, 'I’ve been slowly killing myself and others close to me.

[3] Leslie K. Dunlap closes with, "With its Mississippi setting and sensibility, American Studies scholars will likely soon cite it, particularly the essay "Hip-Hop Stole My Southern Black Boy", as an example of the "New Southern Studies", which places the Black South and regional identity at the center of an analysis of national economic, political, creative, and intellectual narratives".

"[9] In her review for Booklist, Annie Bostram said that the book was, "Gracefully encompassing pain and power and so much in between, Laymon's artfully piercing essays share truth without limit, and could not feel more timely.

"[8] Christopher Romaguera highlights in his review for Emerson College's Ploughshares blog that Kiese Laymon's second release of How to Slowly Kill Yourself and Others in America revisits his essays and invites the reader to reimagine them, offering a more experienced point of view from his home state.

Rosalind Bentley on behalf of The Atlanta Journal-Constitution wrote on the collection that, "Laymon writes that it took courage for him to face himself, the truth of who he is, who he was.