This chapter explores the introduction and rolling out of the separate system in England and Ireland, contextualising this in terms of earlier and rival systems of discipline, notably the silent system. It examines critiques of separate confinement, with vocal opponents often highly critical of the impact of the system on prisoner’s minds, and the extensive debates among prison administrators, governors, chaplains, and medical officers, as to whether separate confinement might provoke cases of mental disorder. Modifications were introduced to the purest form of separate confinement, yet, as we explain, the separate system continued to dominate penal policy and practice, despite persistent concerns about the damage it inflicted on prisoners’ minds. Drawing on examples from individual prisons, including Pentonville and Mountjoy, the chapter examines the management of mental illness among prisoners, and the ways in which power shifted from the chaplains, key advocates of separate confinement from the 1830s, to the medical officers in the 1850s, as the prison medical service became more coherent and regulated.