The book tells of Black's experiences in the hobo underworld, freight-hopping around the western United States and Canada, with the majority of events taking place from the late 1880s to around 1910.

He tells of becoming a thief, burglar, and member of the yegg (safe-cracking) subculture, exploring the topics of crime, criminal justice, vice, addictions, penology, and human folly from various viewpoints, from observer to consumer to supplier, and from victim to perpetrator.

The main criminal activity of Black's life and of the book is thievery, which leads to discussions of various technical aspects of the thief's "trade", including casing of prospects (surveillance of targets), safe-cracking, fencing of stolen goods, the disposal of evidence, maintaining aliases and avoiding attention or traceability, the social networks of criminals, the experiences of being arrested, questioned, and tried, and the experience of doing time in jails and prisons.

He expresses an opinion that drug addiction is more psychological than physical; nevertheless, he also admits that breaking himself of a daily opium habit was the toughest battle of his life.

The book has been adapted to a film titled You Can't Win (in post-production as of January 2020) starring Julia Garner, Jeremy Allen White and Michael Pitt, who co-produced and co-wrote the screenplay.