The "Brethren" are three former judges who are incarcerated at Trumble, a fictional federal minimum security prison located in northern Florida.

Meanwhile, Teddy Maynard, the ruthless and soon-to-retire director of the CIA, is orchestrating a scheme to tip the United States presidential election in the favor of Aaron Lake, a hawkish congressman supported by arms manufacturers.

In a starred review, Publishers Weekly highlighted how Grisham is one of "only a few megaselling authors of popular fiction [who] deviate dramatically from formula".

In line with this praise, they noted that "Grisham's fans may miss the stalwart lawyer-heroes and David vs. Goliath slant of his earlier work", given the fact that "every personage in this novel lies, cheats, steals and/or kills"; however, they concluded that "all will be captivated by this clever thriller that presents as crisp a cast as he's yet devised, and as grippingly sardonic yet bitingly moral a scenario as he's ever imagined".

Club's Tasha Robinson also discussed how "The Brethren presents a curious speed bump in [Grishman's] decade-long ride on literary cruise control", adding that, "most notably, there isn't a single film-friendly hero here".