A difficult divorce, financial problems, mistresses, a mobster; in the troubles of Charlie, a successful writer, the death of his friend and mentor Humboldt is also added. Will the gift he bequeathed to him help? The book earned Bellow the Pulitzer, the year he won the Nobel Prize (1976).

The novel, which Bellow initially intended to be a short story, is a roman à clef about Bellow's friendship with the poet Delmore Schwartz. It explores the changing relationship between art and power in a materialistic America. This theme is addressed through the contrasting careers of two writers, Von Humboldt Fleisher (to some extent a version of Schwartz) and his protégé Charlie Citrine (to some extent a version of Bellow himself). Fleisher longs to elevate American society through art but dies a failure. In contrast, Charlie Citrine makes a lot of money through his writing, especially from a Broadway play and a film about a character named Von Trenck - a character modeled after Fleisher.

Another notable character in the book is Rinaldo Cantabile, an adventurous Chicago gangster who tries to intimidate Citrine into becoming friends. Because his career advice to Citrine is commercially sound, it directly contrasts with the advice of Citrine's former mentor, Humboldt Fleisher, who prioritizes artistic integrity.