The relationship between prisons and mental illness has preoccupied prison administrators, physicians, and reformers from the establishment of the modern prison service in the nineteenth century to the current day. Here we take the case of Pentonville Model Prison, established in 1842 with the aim of reforming convicts through religious exhortation, rigorous discipline and training, and the imposition of separate confinement in its most extreme form. Our article demonstrates how following the introduction of separate confinement, the prison chaplains rather than the medical officers took a lead role in managing the minds of convicts. However, instead of reforming and improving prisoners’ minds, Pentonville became associated with high rates of mental disorder, challenging the institution’s regime and reputation. We explore the role of chaplains, doctors, and other prison officers in debating, disputing, and managing cases of mental breakdown and the dismantling of separate confinement in the face of mounting criticism.