Based on an original idea by best-selling Danish novelist Elsebeth Egholm, the series follows the inquiries of a special unit at Copenhagen's police force, consisting of detective inspector Katrina Ries Jensen and forensic psychiatrist Thomas Schaeffer. The pair specialise in serial killers that do not fit within traditional behavioural patterns.

The R of the title stands for the young protagonist, Rune, fearlessly played by Pilou Asbæk. Imprisoned for violent assault, he's a cocky, good-looking young man placed in the hardcore ward, where his survival depends on quickly learning the prison's parallel world of rules, honor, and obligations. R also stands for Rachid, a young Muslim prisoner who becomes Rune's friend and accomplice, defying the rigid racial stratifications among the inmates.